Filter medium for leukocyte removal, method of making, and method of using thereof

ABSTRACT

A leukocyte-removing filter material is described, which includes a porous element having fine pores of an average pore diameter of not less than 1.0 μm but less than 100 μm and a fiber structure composed of a plurality of fibers having an average fiber diameter of not less than 0.01 μm but less than 1.0 μm kept on the porous element. The porosity of the filter material is not less than 50% but less than 95%, and the proportion of the fiber structure to the filter material is not less than 0.01% by weight but less than 30% by weight. The ratio between the average pore diameter of the porous element and the average fiber diameter of the fiber structure is not less than 2 but less than 2,000 and the above fiber structure forms a reticulate structure. A process for producing the leukocyte-removing fiber material and an apparatus for removing leukocyte using the above fiber material are also described.

TECHNICAL FIELD

This invention relates to a leukocyte-removing filter material forremoving leukocyte from a leukocyte-containing solution, a process forproducing the same, a leukocyte-removing apparatus using the same and aprocess for removing leukocyte.

BACKGROUND ART

In the field of a blood transfusion, in addition to the so-called wholeblood transfusion that a whole blood preparation prepared by adding ananticoagulant to blood gathered from donors is transfused, a so-calledblood component transfusion has heretofore been generally carried out bywhich the blood component which the recipient requires separated fromthe whole blood preparation is transfused into the recipient. The bloodcomponent transfusion includes erythrocyte transfusion, platelettransfusion, plasma transfusion and the like depending upon the kind ofblood component required by a recipient, and the blood componentpreparations used in these transfusions include erythrocyte preparation,platelet preparation, plasma preparation and the like. Recently, aso-called leukocyte-removed blood transfusion has been spread by which ablood preparation is transfused after the leukocyte mixed in the bloodcomponent preparation has been removed. This is because it has beenclarified that relatively light side effects such as headache, nausea,chill, non-hemolytic febrile transfusion reaction and the like whichaccompany the blood transfusion; grave side effects such as alloantigensensitization, virus infection, post-transfusion GVHD and the like whichseriously affect the recipient are caused mainly by the leukocyte mixedin a blood preparation used in the blood transfusion.

In order to prevent the relatively light side effects includingheadache, nausea, chill, fever and the like, it is said that the removalof the leukocyte in a blood preparation until the proportion of theresidual leukocyte becomes 10⁻¹ to 10⁻² or less is sufficient. Also, inorder to prevent the alloantigen sensitization and virus infection whichare grave side effects, it is said that the removal of the leukocyteuntil the proportion of the residual leukocyte becomes 10⁻⁴ to 10⁻⁶ orless is sufficient.

The method of removing leukocyte from a blood preparation is roughlyclassified into two methods, one of which is a centrifuging method bywhich leukocyte is separated and removed by utilizing the specificgravity difference of blood components by using a centrifugal separatorand a filtering method by which leukocyte is removed using a filtermaterial consisting of a porous element such as a fibrous material, aporous material having interconnected cells or the like. The filteringmethod has such advantages as excellent leukocyte-removing performance,simple operation, low cost, etc., so that the filtering method has beenspread. Moreover, as the filtering method, a method which comprisesremoving leukocyte by sticking or adsorbing using a nonwoven fabric as afilter material is now the most spreading because this method isparticularly excellent in leukocyte-removing performance.

The mechanism of removing leukocyte by a filter apparatus using theabove-mentioned fibrous material or porous material is mainly attributedto the fact that the leukocyte which has contacted with the surfaces ofthe filter material sticks to or adheres to the surfaces of the filtermaterial. For example, EP-A-0155003 discloses a technique by which anonwoven fabric is used as the filter material. Furthermore, WO93/01880discloses a leukocyte-removing filter material produced by dispersing ina dispersion medium a mass of a great number of small fiber pieceshaving a fiber diameter of not more than 0.01 μm and a length of about 1to 50 μm, together with spinable and weavable short fibers having afineness of about 0.05 to 0.75 d and an average length of 3 to 15 mm,and removing the dispersion medium from the resulting dispersion.

The existing leukocyte-removing filter has such a leukocyte-removingperformance as to decrease the number of the residual leukocytes to notmore than 1×10⁵. Under such circumstances, two demands for theleukocyte-removing filter have been brought up in the market.

The first demand is to enhance the recovery of the useful component andimprove the handling by rendering the operation of recovering the usefulcomponent remaining in the filter and the circuit unnecessary by thepresence of a physiological saline solution and air. In particular,blood which is the starting material for the blood preparation is inmany cases a precious one supplied by well-intentioned blood donation,and the blood which has remained in the filter and has become impossibleto recover is scrapped as it is, together with the filter and goes towaste. Therefore, it is very significant to increase the recovery of theuseful component as compared with the existing leukocyte-removingfilter. However, in the case of the leukocyte-removing filter using theconventional technique, it is difficult to very greatly increase therecovery of the useful component.

The second demand is to achieve a higher leukocyte-removing rate thanthe existing leukocyte-removing filter and completely prevent a graveside effect from being caused by the leukocyte transfused into apatient. However, with the leukocyte-removing filter using theconventional technique, it is difficult to achieve so high aleukocyte-removing rate that such a side effect can be completelyprevented.

DISCLOSURE OF INVENTION

The first object of this invention is to provide a leukocyte-removingfilter material which is much higher in leukocyte-removing performanceper unit volume than the conventional filter material and in which theflow of a leukocyte-containing solution is good. This filter material isa leukocyte-removing filter material which comprises a porous elementhaving fine pores of an average pore diameter of not less than 1.0 μmbut less than 100 μm and a fiber structure composed of a plurality offibers having an average fiber diameter of not less than 0.01 μm butless than 1.0 μm kept on the above porous element and in which theporosity of the above filter material is not less than 50% but less than95%; the proportion of the above fiber structure to the said filtermaterial (the word "proportion" is called "keeping proportion"hereinafter) is not less than 0.01% by weight but less than 30% byweight; the ratio between the average pore diameter of the pores of theabove porous element (referred to in some cases hereinafter as theaverage pore diameter of the porous element) and the average fiberdiameter of the fibers constructing the above fiber structure (referredto in some cases hereinafter as the average fiber diameter of the fiberstructure) is not less than 2 but less than 2,000; and the above fiberstructure forms a reticulate structure. The present inventors have foundthat when such a leukocyte-removing filter material is used, theabove-mentioned first object can be achieved.

The second object of this invention is to provide a process forproducing the leukocyte-removing filter material of this invention. Thisprocess is a process for producing a filter material in which fibershaving an average fiber diameter of not less than 0.01 μm but less than1.0 μm obtained by cleaving cleavable fibers are dispersed in a solventand deposited and kept on a porous element having fine pores of anaverage pore diameter of not less than 1.0 μm but less than 100 μm(referred to in some cases hereinafter as the porous element having anaverage pore diameter of not less than 1.0 μm but less than 100 μm); aprocess for producing a filter material comprising allowing amicroorganism having an ability to produce cellulose fiber and a porouselement having an average pore diameter of not less than 1.0 μm but lessthan 100 μm to coexist in a liquid culture medium and culturing themicroorganism; or the like. The present inventors have found thataccording to such a process, the leukocyte-removing filter material ofthis invention can be produced very effectively.

The third object of this invention is to provide a filter apparatus forremoving leukocyte which can remove leukocyte from aleukocyte-containing solution such as a whole blood preparation, anerythrocyte preparation, a platelet preparation or the like whileinhibiting the loss of the useful blood component very low, and achievea high leukocyte-removing rate; and a process for removing leukocyte.The present inventors have found that when a leukocyte-containingsolution is filtered by means of the filter apparatus for removingleukocyte in which a leukocyte-removing filter material is appropriatelyarranged which consists of a porous element having an average porediameter of not less than 1.0 μm but less than 100 μm and a fiberstructure composed of a plurality of fibers having an average fiberdiameter of not less than 0.01 μm but less than 1.0 μm kept on the aboveporous element (said fiber structure is referred to hereinafter as thefiber structure having an average fiber diameter of not less than 0.01μm but less than 1.0 μm) and in which the porosity of the filtermaterial is not less than 50% but less than 95%; the keeping proportionof the above fiber structure to the above filter material is not lessthan 0.01% by weight but less than 30% by weight; the ratio between theaverage pore diameter of the above porous element and the average fiberdiameter of the above fiber structure is not less than 2 but less than2,000; and the above fiber structure forms a reticulate structure, theloss of the useful blood component can be lowered and a highleukocyte-removing rate can be achieved.

The present inventors have made extensive research in order to achievethe above objects, and have consequently completed this inventionrelating to a leukocyte-removing filter material which consists of aporous element having an average pore diameter of not less than 1.0 μmbut less than 100 μm and a fiber structure of an average fiber diameterof 0.01 μm but less than 1.0 μm kept on the above porous element and inwhich the porosity of the above filter material is not less than 50% butless than 95%; the keeping proportion of the above fiber structure tothe above filter material is not less than 0.01% by weight but less than30% by weight; the ratio between the average pore diameter of the aboveporous element and the average fiber diameter of the above fiberstructure is not less than 2 but less than 2,000; and the above fiberstructure forms a reticulate structure.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is an electron micrograph of a filter material having a curvedreticulate structure.

FIG. 2 is an electron micrograph of a filter material having a polygonalreticulate structure.

FIG. 3 is an electron micrograph of a nonwoven fabric filter material inwhich fibers having different fiber diameters are mixed and entangled.

BEST MODE FOR CARRYING OUT THE INVENTION

The average fiber diameter referred to in this invention is a valueobtained by taking a scanning electron micrograph of fibers constructingthe fiber structure, measuring diameters of at least 100 fibers selectedat random and calculating the number average value of them. Themeasurement of the average fiber diameter may be carried out beforekeeping the fibers on the porous element which is a base material orafter keeping the fibers on the porous element which is a base material.In particular, when the porous element is composed of a congregation offibers, it is preferable to measure the average fiber diameter beforekeeping the fibers on the porous element because the measurement can bemore exactly carried out.

Fibers having an average fiber diameter of less than 0.01 μm have a lowfiber strength, and when a leukocyte-containing solution is treated, thefibers tend to be cut by collision of leukocyte, other blood cellcomponents or the like, so that the above fibers are not suitable forthe purpose of this invention. Moreover, fibers having an average fiberdiameter of not less than 1.0 μm make the porosity of the filtermaterial smaller, whereby the flow of a leukocyte-containing solutionbecomes bad, so that the above fibers are not suitable for the purposeof this invention. In order to contact lymphocyte and the like, whichhave a relatively small diameter among the leukocytes and are low intackiness, with the filter material at many points with a goodefficiency and capture them, the average fiber diameter of the fibers ispreferably not less than 0.01 μm but less than 0.8 μm.

In addition, in the fiber structure in this invention, fibers having avery small average fiber diameter form a reticulate structure. Such areticulate fiber structure is kept on the porous element. In thisinvention, that the fiber structure is kept on the porous element meansthe state that the above reticulate fiber structure is present so thatthe pore portions of the porous element which is a base material arecovered therewith and is fixed on the base material as shown in FIG. 1or FIG. 2. FIG. 1 and FIG. 2 are electron micrographs of the filtermaterials of this invention having typical reticulate structures. Basedon FIG. 1 and FIG. 2, the characteristics in physical structure of thefilter material of this invention are described below.

In the filter material of this invention, a plurality of fibers havingan average fiber diameter of not less than 0.01 μm but less than 1.0 μmform a reticulate structure and constitute the fiber structure, and thisfiber structure is kept on a porous element having fine pores having anaverage pore diameter of not less than 1.0 μm but less than 100 μm.However, the fibers constituting the fiber structure are not in the forma bundle but in the form of a so-called single fiber in which the fibersare in the split state, and a plurality of these single fibers arephysically entangled to form a reticulate structure. The reticulatestructure referred to in this invention includes such a structure thatthe formed meshes are curved because the fibers constituting the fiberstructure have a curved structure as represented by FIG. 1, and such astructure that the meshes formed are polygonal because the fibersconstituting the fiber structure have a linear structure as representedby FIG. 2.

When this reticulate fiber structure is uniformly kept on the porouselement at the cross-section perpendicular to the flow of theleukocyte-containing solution, the leukocyte can be captured with a goodefficiency, so that it is preferred. That the fiber structure isuniformly kept on the porous element at the cross-section perpendicularto the flow of the leukocyte-containing solution means that whenportions of filter material in the cross-section perpendicular to theflow of the leukocyte-containing solution are sampled at random, theamount (density) of the fiber structure contained in each of thosesampled portions of filter material is substantially equal, and thisamount introduced can be actually determined by measuring the scatteringof amount of the fiber structure present in a given amount of the filtermaterial in each portion of the filter material sampled.

Furthermore, it is particularly preferable that in addition to thesubstantially equal amount of the fiber structure introduced in eachportion of the filter material sampled at random in the cross-sectionperpendicular to the flow of the leukocyte-containing solution, thedistribution of mesh sizes in each portion is substantially equal and asubstantially same reticulate structure is formed. Incidentally, in thepresent specification, such a state is expressed "a uniform, reticulatestructure is formed". More specifically explaining, that a uniform,reticulate structure is formed refers to such a state that thereticulate structure in each portion of the filter material sampled atrandom has, when observed through an electron microscope, a distributionof approximate mesh sizes and a similar mesh form and is deemed to besubstantially the same. The state that no uniform reticulate structureis formed refers to such a state that when the reticulate structure ineach portion of the filter material sampled at random is observed, itcan be judged that the distribution of mesh sizes in each portion isgreatly different and the form thereof is clearly different.

In the filter material of this invention, it is preferable that thefiber structure having an average fiber diameter of not less than 0.01μm but less than 1.0 μm forms a reticulate structure and is kept on theporous element having an average pore diameter of not less than 1.0 μmbut less than 100 μm; the porosity of the filter material is not lessthan 50% but less than 95%; and the ratio between the average porediameter of the porous element and the average fiber diameter of thefiber structure is not less than 2 but less than 2,000.

Here, the average pore diameter is a value obtained by measurementaccording to a mercury pressurizing method. That is to say, when theamount of mercury pressurized at a mercury-pressurizing pressure of 1psia is 0% and the amount of mercury pressurized at a mercurypressurizing pressure of 265 psia is 100%, a fine pore diametercorresponding to an amount of mercury pressurized of 50% is taken as theaverage pore diameter. When the average pore diameter is less than 1.0μm, the leukocyte-containing solution does not flow and hence it is notsuitable for the purpose of this invention. When the average porediameter is not less than 100 μm, it often becomes difficult to maintainthe fiber structure and hence it is not suitable for the purpose of thisinvention.

In order to keep the flow of the leukocyte-containing solution in a goodstate, the ratio between the average pore diameter of the porous elementand the average fiber diameter of the fiber structure is preferably notless than 2 but less than 2,000. When the ratio between the average porediameter of the porous element and the average fiber diameter of thefiber structure is less than 2, there is substantially no differencebetween the fine pore diameter of the porous element and the diametersof fibers constituting the fiber structure and the fine pores of theporous element are blocked with the fibers and consequently the flow ofthe leukocyte-containing solution becomes very bad. Therefore, it is notsuitable for the purpose of this invention. When the ratio of theaverage pore diameter of the porous element and the average fiberdiameter of the fiber structure is not less than 2,000, the diameters offine pores of the porous element are large and it becomes difficult tokeep the fiber structure so that the fine pores of the porous elementare covered with the fiber structure and an extreme decrease of theleukocyte-removing performance is brought about. In addition thereto,the entanglement of the fiber structure with the porous element becomesinsufficient and there is a fear that the fiber structure falls away, sothat it is not suitable. It is more preferable that the ratio betweenthe average pore diameter of the porous element and the average fiberdiameter of the fiber structure is not less than 10 but less than 1,800.

The porous element referred to in this invention includes a fibercongregation, a porous film, a spongy, interconnected, porous materialand the like which have an average pore diameter of not less than 1 μmbut less than 100 μm. As the porous element, preferable is the abovefiber congregation, particularly preferable is a fiber congregationconsisting of long fibers. The form of the fiber congregation ispreferably a nonwoven fabric, a woven fabric, a knitted fabric or thelike; however, particularly preferable is a nonwoven fabric. When theporous element is a fiber congregation, it is particularly preferablethat the ratio of the average fiber diameter of the fiber congregationto the average fiber diameter of the fiber structure is not less than 10but less than 1,000 in order to keep the flow of theleukocyte-containing solution in a good state. As the material of theporous element, there can be used any material which can form a nonwovenfabric, a woven fabric, a knitted fabric, a porous film, a spongy,interconnected, porous material or the like, such as polyurethane,polyester, polyolefin, polyamide, polystyrene, polyacrylonitrile,cellulose, cellulose acetate or the like.

Moreover, in the leukocyte-removing filter material of this invention,it is preferable that the keeping proportion of the fiber structure tothe filter material is not less than 0.01% by weight but less than 30%by weight. When the keeping proportion is less than 0.01% by weight,there is not obtained a sufficient amount of fibers for capturing theleukocyte in a leukocyte-containing solution, so that it is not suitablefor the purpose of this invention. When the keeping proportion is notless than 30% by weight, the amount of fibers introduced into the porouselement becomes too large, and the fine pore portions of the porouselement are blocked, whereby the leukocyte-containing solution does notflow, so that it is not suitable for the purpose of this invention. Thekeeping proportion of the fiber structure to the filter material is morepreferably not less than 0.03% by weight but less than 10% by weight.

The measurement of the keeping proportion can be determined from theweight change before and after keeping the fiber structure on the porouselement. Also, when the keeping proportion of the fiber structure is assmall as less than about 3% by weight per unit weight of the filtermaterial, there can be used, for more precisely determining the keepingproportion of the fiber structure than the above weight measurement, amethod by which only the fiber structure is dissolved and abstracted andthe amount of the abstracted component is determined. Referring to thecase where the fiber structure is composed of cellulose as an example, amethod of determining the amount thereof is specifically explainedbelow. The leukocyte-removing filter material of this invention isimmersed and shaken in a solution of cellulase to decompose thecellulose of the fiber structure into glucose and the glucose isextracted. The extracted glucose is subjected to quantitativedetermination using a commercially available quantitative determinationreagent, and from the amount of glucose obtained, the amount of fiberstructure kept on the porous element is calculated.

In order to achieve a high leukocyte-removing performance, it ispreferable that the fiber structure is kept over the whole of the porouselement. However, when it is difficult that the fiber structure is keptin a deep interior of the porous element because of a limit resultingfrom production process, the fiber structure may be kept on the surfaceof one side of the porous element, and in such a case, as a means forsimply enhancing the leukocyte-removing performance of the filtermaterial by increasing the keeping proportion of the fiber structure,the fiber structure may be kept on the surfaces of both sides of theporous element. In either case, it is preferable to substantiallyuniformly keep the fiber structure on the porous element in order toachieve the high leukocyte-removing performance.

In the leukocyte-removing filter material of this invention, it ispreferable that the porosity is not less than 50% but less than 95%.When the porosity of the filter material is less than 50%, the flow ofthe leukocyte-containing solution is bad and it is not suitable for thepurpose of this invention. When the porosity is not less than 95%, themechanical strength of the filter material is low and when theleukocyte-containing solution is treated, the filter material is brokenand no more exerts its function as a filter material, so that it is notsuitable for this invention.

The porosity is determined by measuring the dry weight (W₁) of thefilter material cut to the given area; further measuring the thickness;calculating the volume (V), immersing this filter material in water,subjecting the same to deaeration; thereafter measuring the weight (W₂)of the water-containing filter material; and calculating the porosityfrom the following calculating equation in which ρ is the density ofpure water:

    Porosity (%)=(W.sub.2 -W.sub.1)×ρ×100/V.

The thickness of the leukocyte-removing filter material of thisinvention is preferably not less than 0.1 mm but less than 30 mm in thedirection of the flow of the leukocyte-containing solution. When thethickness is less than 0.1 mm, the frequency of collision between thefilter material and the leukocyte in the leukocyte-containing solutionis reduced, and hence, a high leukocyte-removing performance isdifficult to achieve, so that it is not desirable. When the thickness isnot less than 30 mm, the resistance of the filter material to thepassing of the leukocyte-containing solution therethrough becomes high,and hence, the treatment time is elongated and the erythrocyte membraneis broken to cause hemolysis, and for these reasons and the like, it isnot desirable. It is more preferable that the thickness of the filtermaterial in the flow direction is not less than 0.1 mm but less than 15mm.

When as a method of obtaining the filter material of this invention,there is adopted a production process characterized by dispersing thefibers having an average fiber diameter of not less than 0.01 μm butless than 1.0 μm in a solvent and keeping the same, by paper-making, ona porous element having an average pore diameter of not less than 1.0 μmbut less than 100 μm, it is more preferable that in theleukocyte-removing filter material obtained, the ratio of the averagepore diameter of the porous element to the average fiber diameter of thefiber structure is not less than 16 but less than 300. Moreover, thekeeping proportion of the fiber structure to the filter material ispreferably not less than 0.3% by weight but less than 5.0% by weight. Inaddition, it is more preferable that the average fiber diameter of thefiber structure is not less than 0.05 μm but less than 0.5 μm.

Furthermore, when as a method of obtaining the filter material of thisinvention, there is adopted a production process characterized byallowing a microorganism having an ability to produce cellulose fiberand a porous element having an average pore diameter of not less than1.0 μm to less than 100 μm to coexist in a liquid culture medium,culturing the microorganism in the liquid culture medium and recoveringthe porous element, it is preferable that in the leukocyte-removingfilter material obtained, the ratio of the average pore diameter of theporous element to the average fiber diameter of the fiber structure isnot less than 160 but less than 1,500. In addition, it is morepreferable that the keeping proportion of the fiber structure to thefilter material is not less than 0.03% by weight but less than 1.0% byweight, and it is more preferable that the average fiber diameter of thefiber structure is not less than 0.01 μm but less than 0.05 μm.

Since when the leukocyte-removing filter material of this invention istreated, as a post-processing, with a binding agent such as awater-insoluble high polymer solution or the like, there is generally apossibility that the reticulate structure is broken, including the casewhere the fibers constructing the fiber structure are bundled with oneanother in the form of a bundle, the case where a film-like material isformed between plural fibers, and the like, so that it is preferablethat the filter material is not treated with such a binding agent. Onthe other hand, when the fibers are relatively thick and short and thephysical entanglement thereof with the porous element is insufficient,it is possible to effectively fix the fibers on the porous element by atreatment with a binding agent such as a relatively dilute,water-insoluble high polymer solution or the like as a post-processingof the leukocyte-removing filter material of this invention, whereby thefibers can be prevented from falling off.

It is also possible to modify the surface of the leukocyte-removingfilter material to a surface to which platelet or erythrocyte isdifficult to stick, thereby increasing the recovery of the platelet orerythrocyte and removing only the leukocyte. As a method of modifyingthe surface of the filter material, there are mentioned a surfacegraft-polymerization, a coating with a high polymer material, anelectrical discharge treatment and the like.

As the high polymer material used when the surface of the filtermaterial is modified by a surface graft-polymerization or a coating witha high polymer material, preferred is a high polymer material having anonionic hydrophilic group. As the nonionic hydrophilic group, there arementioned hydroxyl group, amido group, polyethylene oxide chain and thelike. The monomers which can be used in the synthesis of the highpolymer material having a nonionic hydrophilic group include, forexample, 2-hydroxyethyl methacrylate, 2-hydroxyethyl acrylate, vinylalcohol (prepared by hydrolyzing a polymer obtained by polymerization ofvinyl acetate), methacrylamide, N-vinylpyrrolidone and the like. Amongthe above monomers, 2-hydroxyethyl methacrylate and 2-hydroxyethylacrylate are preferred in view of easy availability, easy handling inthe polymerization, leukocyte-containing solution-treating performance,and the like.

The high polymer material used in the above surface graft-polymerizationor in the coating with a high polymer material is preferably a copolymercontaining, as a monomeric unit, a polymerizable monomer having anonionic hydrophilic group and/or a basic nitrogen-containing functionalgroup in an amount of 0.1 to 20 mole %. As the basic nitrogen-containingfunctional group, there are mentioned primary amino group, secondaryamino group, tertiary amino group, quaternary ammonium group and thelike; and also nitrogen-containing aromatic ring group such as pyridylgroup, imidazole group and the like; etc. As the polymerizable monomerhaving a basic nitrogen-containing functional group, there can bementioned derivatives of methacrylic acid such as dimethylaminoethylmethacrylate, diethylaminoethyl methacrylate, dimethylaminopropylmethacrylate, 3-dimethylamino-2-hydroxypropyl methacrylate and the like;vinyl derivatives of nitrogen-containing aromatic compounds such asallylamine, p-vinylpyridine, 4-vinylimidazole and the like; andquaternary ammonium salts obtained by reacting the above vinyl compoundwith an alkyl halide or the like. Among the above polymerizablemonomers, dimethylaminoethyl methacrylate and diethylaminoethylmethacrylate are preferred from the viewpoints of easy availability,easy handling in polymerization, leukocyte-containing solution-treatingperformance and the like.

When the monomer unit content of the polymerizable monomer having abasic nitrogen-containing functional group in the copolymer obtained isless than 0.1%, the effect of inhibiting platelet from sticking to thesurface of the filter material is not so much found, and hence, it isnot desirable. Moreover, when the monomer unit content of thepolymerizable monomer having a basic nitrogen-containing functionalgroup in the copolymer is not less than 20%, not only leukocyte but alsouseful components such as platelet and erythrocyte become liable tostick to the surface of the filter material, and hence, it is notdesirable. It is more preferable that the content of the polymerizablemonomer having a basic nitrogen-containing functional group in thecopolymer is 0.2 to 5% as the monomer unit.

The present inventors have made extensive research on providing aprocess for producing a leukocyte-removing filter material which is thesecond object of this invention and have consequently found that whenfibers having an average fiber diameter of not less than 0.01 μm butless than 1.0 μm are dispersed in a dispersion medium and kept, bypaper-making, on a porous element having an average pore diameter of notless than 1.0 μm but less than 100 μm, there can be produced aleukocyte-removing filter material which consists of the above porouselement and a fiber structure composed of a plurality of the fibers andin which the porosity of the above filter material is not less than 50%but less than 95%, the keeping proportion of the above fiber structureto the above filter material is not less than 0.01% by weight but lessthan 30% by weight, the ratio between the average pore diameter of theabove porous element and the average fiber diameter of the above fiberstructure is not less than 2 but less than 2,000 and the above fiberstructure forms a reticulate structure, and have completed theproduction process of this invention.

In order for the fiber structure to form a reticulate structure in thefilter material of this invention, it is necessary that the fibershaving an average fiber diameter of not less than 0.01 μm but less than1.0 μm have a curved shape and have such properties that the fibers perse are soft, easy to curve, relatively short and the like. In addition,even if fibers originally do not have a curved shape, they areapplicable to this invention as far as they have been given a curvedshape by a heat treatment, a mechanical treatment or a treatment withvarious chemicals.

The above fibers having an average fiber diameter of not less than 0.1μm but less than 1.0 μm can be produced by subjecting dividable fibers,representatives of which are regenerated cellulose fiber, finely porouscleavable acrylic fiber and the like, as well as the cleavable compositefibers obtained by the known methods stated in JP-B-47-37648,JP-A-50-5650, JPA-53-38709 and the like, to physical stir using a mixeror the like, ejection of a high pressure liquid stream, treatment in ahigh pressure homogenizer, or the like.

As the material of fiber which can be easily curved, suitable arecellulose, polyacrylonitrile, polyester, polyolefin, polyamide and thelike; however, there can be used any material which can be formed intofibers which have an average fiber diameter of not less than 0.01 μm butless than 1.0 μm and can be curved by a heat treatment or a mechanicaltreatment.

A method for obtaining fibers having the above specified average fiberdiameter by subjecting, among the above-mentioned dividable fibers,regenerated cellulose fibers, if necessary, to acid treatment or alkalitreatment and thereafter to physical stir in a liquid using a mixer orthe like to fibrillate the fibers is particularly preferable, becausethe fiber diameters of the resulting fibers become very small, andfibers having a curved form can be easily obtained, as a result of whichit becomes easy for the fibers to form a reticulate structure. Thisprocess for obtaining fibers having an average fiber diameter of notless than 0.01 μm but less than 1.0 μm by fibrillating regeneratedcellulose fibers is explained below specifically and in more detail.First of all, commercially available regenerated cellulose fibers havingfiber diameters of about 10 μm are cut to a given length, and thereafterimmersed in about 3% by weight aqueous sulfuric acid solution andsubjected to acid treatment at 70° C. for 30 minutes with slowlystirring. The thus acid-treated regenerated cellulose fibers are washedwith water and thereafter vigorously stirred in water using a mixer at10,000 rpm for a period of from 30 minutes to 90 minutes, upon which theregenerated cellulose fibers are fibrillated and made finer, whereby theobjective fibers can be finally obtained.

Also, fibers having an average fiber diameter of not less than 0.01 μmbut less than 1.0 μm obtained by using a known sea-island type fibers asthe starting material, subjecting them, if necessary, to previous heattreatment or mechanical treatment to process the starting fibers into acurved shape and dissolving the sea component using various solvents toremove the same, have also a curved shape and are suitable for theproduction of the above-mentioned leukocyte-removing filter material ofthis invention.

Other processes for obtaining fibers suitable for the production of theleukocyte-removing filter material of this invention are describedbelow.

Microorganisms having an ability to produce cellulose are cultured byintermittently or continuously giving them a vibration in a liquidculture medium. When a vibration is given, the microorganisms having anability to produce cellulose can cut and separate the cellulose fibersproduced from the bacterial cells. In general, with acetic acidbacterium which is a kind of microorganism having an ability to producecellulose, it is said that the fiber diameters of the cellulose fibersproduced are about 0.01 μm to about 0.1 μm and the cellulosefiber-production rate is about 2 μm/min. Accordingly, by suitablysetting the time for which a vibration is given to the liquid culturemedium and the interval thereof, fibers having the desired length can beobtained. By recovering these fibers from the culture medium, there canbe also obtained fibers suitable for the production of theleukocyte-removing filter material of this invention. Furthermore, inorder to enhance the dispersibility of the fibers obtained byintermittently or continuously giving a vibration to microorganismshaving an ability to produce cellulose while culturing themicroorganisms in a liquid culture medium, it is preferable to split thefibers by such a means as violently stirring of the liquid culturemedium or the like. Also, when the microorganisms having an ability toproduce cellulose are continued to be cultured in a liquid culturemedium for a long period of time, a gel-like fiber mass in which anumber of cellulose fibers congregate is obtained. By finely grindingand splitting this gel-like fiber mass in a homogenizer or the like,fibers suitable for the production of the leukocyte-removing filtermaterial of this invention can also be obtained.

The thus obtained fibers having an average fiber diameter of not lessthan 0.01 μm but less than 1.0 μm are dispersed in a dispersion mediumso that the concentration becomes about 0.01 g/L to about 1 g/L toobtain a fiber dispersion. As the dispersion medium, there can be usednot only pure water but also an aqueous solution containing about 0.1%to 5% of a surfactant; an aqueous solution whose viscosity has beenincreased by adding thereto about 0.1% to 5% of a polyacrylamide formore improving the dispersibility of the fibers; and the like.

Subsequently, a porous element having an average pore diameter of notless than 1.0 μm but less than 100 μm is arranged on the base of afunnel-like vessel and the above fiber dispersion is poured thereinto,stored therein for a short while and then discharged at one time, andthereafter the porous element is dried, whereby the filter material ofthis invention can be obtained. In this invention, such a productionprocess is referred to as paper-making. At this time, if the fibers areshort they can be kept even in a deep interior of the porous element, sothat is preferable.

It is preferable to further apply a high pressure liquid streamtreatment at a pressure of about 3 kg/cm² to 200 kg/cm² to the filtermaterial produced by the above-mentioned production process because thefibers can be more uniformly kept in a deeper interior of the porouselement in the direction of the thickness thereof.

As a different preferable process for producing the leukocyte-removingfilter material of this invention, there is mentioned a process whichcomprises allowing a microorganism having an ability to producecellulose fiber and a porous element having an average pore diameter ofnot less than 1.0 μm but less than 100 μm to coexist in a liquid culturemedium, culturing the microorganism in the liquid culture medium andthereafter recovering the porous element. Even by this process, therecan be produced a leukocyte-removing filter material in which a fiberstructure having an average fiber diameter of not less than 0.01 μm butless than 1.0 μm are kept on the porous element, the porosity of thefilter material is not less than 50% but less than 95%, the keepingproportion of the fiber structure to the above filter material is notless than 0.01% by weight but less than 30% by weight, the ratio betweenthe average pore diameter of the porous element and the average fiberdiameter of the fiber structure is not less than 2 but less than 2,000and the fiber structure forms a reticulate structure. An example of thisproduction process is specifically explained below.

First of all, a porous element as a base material is arranged in aculture medium. The composition of a representative culture medium is 2%of grape sugar, 0.5% of polypeptone, 0.5% of yeast extract, 0.27% ofsodium hydrogenphosphate anhydride and 0.115% of citric acidmonohydrate. It is sufficient that the porous element is partlycontacted with at least the culture medium, and it is preferable thatthe porous element is arranged in parallel to the surface of the culturemedium. A microorganism having an ability to produce cellulose fiber isdispersed in the culture medium so that the microorganism concentrationbecomes not less than 1 cell/mL but less than 1.0×10⁷ cells/mL. In thisstate, the microorganism is cultured for a period of 0.5 hour to 48hours to keep a reticulate fiber structure composed of cellulose fiberson the porous element, thereby producing the leukocyte-removing filtermaterial of this invention. The microorganism having an ability toproduce cellulose fiber is inferred to produce cellulose fibers while itwanders in the interior of the porous element, and hence, a reticulatestructure of long cellulose fibers is kept in the interior of the porouselement in such a state that the fibers are physically and closelyentangled. Accordingly, even when the filter material is washed or theleukocyte-containing solution is allowed to flow down in the filtermaterial, the reticulate structure of the cellulose fibers is not brokenand does not fall off. Moreover, by controlling the concentration of themicroorganism having an ability to produce cellulose fiber in theculture medium, the culturing time and the like, the amount of thecellulose fibers kept on the porous element can be controlled. Forexample, when the concentration of the microorganism in the culturemedium at the time of starting the culture is the same, the keepingproportion is increased by prolonging the culturing time. When theculturing time is the same, the keeping proportion is increased byelevating the concentration of the microorganism in the culture mediumat the time of starting the culture.

As the microorganism having an ability to produce cellulose fiber, therecan be utilized acetic acid bacteria of the Acetobacter genus, bacteriaof the Sarcina genus, bacteria of the Bacterium genus, bacteria of theAgrobacterium genus, bacteria of the Rhizobium genus, bacteria of thePseudomonas genus, and the like. Among them, acetic acid bacteria of theAcetobacter genus are particularly preferable. The microorganisms of theAcetobacter genus are said to produce fibers having a fiber diameter of0.01 μm to 0.1 μm; however, the use of other microorganisms mentionedabove enables the production of fibers having various fiber diameters.When, among the culture medium components, the amounts of thepolypeptone which is the nitrogen source and the yeast extract areincreased or decreased, the division and proliferation potential of themicroorganism can be inhibited, whereby the mesh size of the fiberstructure formed can be controlled.

As mentioned hereinbefore, when the microorganism having an ability toproduce cellulose fiber is given a vibration during culturing, it cutsthe cellulose fibers produced from the bacterial cells in some cases,and hence, in order to keep the reticulate fiber structure on the porouselement with a good efficiency in the state that the fibers arephysically and closely entangled, it is preferable that the culture is astationary culture. In addition, when the culture is effected while theliquid level of the liquid culture medium is changed intermittently orcontinuously to allow the liquid culture medium to pass through theexterior and interior of the porous element, the reticulate fiberstructure can be kept in the interior of the porous element with a goodefficiency. In general, microorganisms having an ability to producecellulose fiber are aerobic bacteria and when they are cultured while agas is fed into the liquid culture medium and/or the interior of theporous element, the ability to produce cellulose fiber is enhanced andthe filter material can be produced with a better efficiency. When themicroorganisms having an ability to produce cellulose fiber are aerobicbacteria, the existing density of the microorganism tends to become highin the portion in which the dissolved oxygen concentration is relativelyhigh in the neighborhood of the surface of the culture medium.Therefore, in the case of the filter material of this invention producedby carrying out the stationary culture in such a state that the porouselement is arranged in parallel to the surface of the culture medium andsunk under the surface of the culture medium, the keeping proportion ofthe reticulate fiber structure tends to become higher on the uppersurface of the porous element. In order to increase theleukocyte-removing performance of the filter material, it is preferableto increase the keeping proportion of the reticulate fiber structureand, for example, it is possible to increase the keeping proportion onthe lower surface of the porous element by turning the porous elementupside down during the culture.

In order to control the amount of cellulose fibers which can be kept onthe porous element by controlling the concentration of the microorganismhaving an ability to produce cellulose fiber in the culture medium andthe culturing time, it is preferable that the microorganismconcentration is not less than 1 cell/mL but less than 1.0×10⁷ cells/mLand the culturing time is not less than 0.5 hour but less than 48 hours.When the microorganism concentration is less than 1 cell/mL, the keepingproportion of fibers becomes small in many cases and theleukocyte-removing performance of the filter material becomes low, sothat it is not desirable. When the microorganism concentration is notless than 1.0×10⁷ cells/mL, the keeping proportion of the fibers becomeslarge in many cases and the flow of the leukocyte-containing solution inthe filter material becomes bad, so that it is not desirable. As amethod of determining the number of microorganism cells having anability to produce cellulose fiber in the culture medium, a colonycounting method can be used. When the culturing time is less than 0.5hour, the keeping proportion of the reticulate fiber structure is smallin many cases, and it is impossible to achieve a high leukocyte-removingperformance, so that it is not desirable. When the culturing time is notless than 48 hours, a portion in which the keeping proportion of thereticulate fiber structure is extremely large, namely a skin layer-likestructure is formed in many cases on the surface of the porous elementand the flow of the leukocyte-containing solution becomes bad, so thatit is not desirable.

As a further different process for producing the leukocyte-removingfilter material of this invention, there can be mentioned a process forproducing a leukocyte-removing filter material in which the reticulatefiber structure is kept on the porous element, the porosity of thefilter material is not less than 50% but less than 95%, the keepingproportion of the fiber structure to the filter material is not lessthan 0.01% by weight but less than 30% by weight and the ratio betweenthe average pore diameter of the porous element and the fiber diameterof the fiber structure is not less than 2 but less than 2,000, whichcomprises spinning a porous element having an average pore diameter ofnot less than 1.0 μm but less than 100 μm by the melt-blowing processand mixing fibers having an average fiber diameter of not less than 0.01μm but less than 1.0 μm into the fiber bundle stream which is beingspun. It is preferable that the leukocyte-removing filter materialproduced by the above production process is subjected to a high pressureliquid stream treatment at about 3 kg/cm² to about 200 kg/cm² because itis made possible to keep the fibers more uniformly and in a deeperinterior of the porous element.

The third object of this invention is to provide an apparatus forremoving leukocyte which makes it possible to remove the leukocyte fromthe leukocyte-containing solution while inhibiting the loss of theuseful blood components in a very low state and achieve a highleukocyte-removing rate and to provide a process for removing leukocyteusing the apparatus as well as to provide an apparatus for removingleukocyte which can achieve a much higher leukocyte-removing rate thanconventional apparatus for removing leukocyte and a process for removingleukocyte using the same. The present inventors have made extensiveresearch and have consequently found that the above object can beachieved by filtering a leukocyte-containing solution using a filterapparatus in which the filter material of this invention isappropriately arranged in a vessel having at least a feed opening and adischarging opening.

The filter apparatus for removing leukocyte of this invention is anapparatus in which a filter comprising the filter material of thisinvention is appropriately packed in a vessel having at least a feedopening and a discharging opening. One filter material layer or pluralfilter material layers laminated in the flow direction of theleukocyte-containing solution may be packed in the vessel. On the otherhand, in the case where a high polymer material-containing solution ispoured into a filter material for the purpose of modifying the surfaceof the filter material to subject the surface to coating treatment or inthe like case, the filter material in the lowest layer in the apparatusof this invention sticks onto the internal wall of the apparatus tocause a drift of the leukocyte-containing solution in some cases. Insuch a case, by inserting a relatively large mesh filter material intothe lowest layer, the filter material can be prevented from stickingonto the internal wall of the vessel to cause a drift of theleukocyte-containing solution.

The filter apparatus for removing leukocyte of this invention mayfurther contain other filter materials on the upper stream side and/orthe downstream side of the filter material of this invention.

In general, the leukocyte-containing solution contains fine aggregatesin many cases. In order to remove leukocyte from a leukocyte-containingsolution which contains a large amount of such fine aggregates, aprefilter can be used. As the prefilter, there are preferably used acongregate of fibers having an average fiber diameter of 8 μm to 50 μm;an interconnected porous material having an average pore diameter of 20μm to 200 μm; and the like.

It is preferable that the sectional area of the filter material in thenormal line direction to the flow direction of the leukocyte-containingsolution in the filter apparatus for removing leukocyte of thisinvention is not less than 3 cm² but less than 100 cm². When thesectional area is less than 3 cm², the flow of the leukocyte-containingsolution becomes extremely bad, so that it is not desirable. When thesectional area is not less than 100 cm², the thickness of the filter hasto be made small and a high leukocyte-removing performance cannot beachieved. In addition thereto, the size of the filter apparatus isrequired to be made large, so that it is not desirable.

The process for removing leukocyte of this invention comprises treatinga leukocyte-containing solution in the filter apparatus for removingleukocyte of this invention and recovering the filtered solution. Inmore detail, it is a process for removing leukocyte from aleukocyte-containing solution which comprises using an apparatushaving 1) a feed opening, 2) a filter comprising the filter material ofthis invention and 3) a discharge opening, pouring aleukocyte-containing solution from the feed opening and recovering thesolution filtered through the filter material from the dischargeopening.

As the leukocyte-containing solution to be filtered in the filterapparatus for removing leukocyte of this invention, there are mentioneda whole blood preparation, a concentrated erythrocyte preparation, aplatelet concentrate preparation and, in addition, a body fluid and thelike.

When the leukocyte-containing solution is a whole blood preparation or aconcentrated erythrocyte preparation, it is preferable to treat theleukocyte-containing solution in a filter apparatus for removingleukocyte having an apparatus volume of not less than 3 mL but less than20 mL per one unit. Here, the term "one unit" refers to about 300 mL to550 ml of a whole blood preparation or a concentrated erythrocytepreparation. When the apparatus volume per one unit is less than 3 mL,the possibility that a high leukocyte-removing rate cannot be achievedis high, so that it is not desirable. When the apparatus volume per oneunit is not less than 20 mL, the amount of the useful components in theleukocyte-containing solution remaining unrecovered in the apparatus, inother words, the loss of the useful components becomes large, so that itis not desirable. By filtering the whole blood preparation or theconcentrated erythrocyte preparation in the filter apparatus forremoving leukocyte of this invention, the leukocyte can be removed untilthe number of the residual leukocytes in the recovered solution becomesless than 1×10³ leukocytes/unit.

When the leukocyte-containing solution is a platelet concentratepreparation, it is preferable to treat the leukocyte-containing solutionin a filter apparatus for removing leukocyte having an apparatus volumeper 5 units of not less than 1 mL but less than 10 ml. Here, the term "5units" refers to about 170 mL to about 200 mL of a platelet concentratepreparation. When the apparatus volume per 5 units is less than 1 mL,the possibility that a high leukocyte-removing rate cannot be achievedis high, so that it is not desirable. When the apparatus volume per 5units is not less than 10 mL, the amount of the useful componentsremaining unrecovered in the apparatus becomes large, so that it is notdesirable. By filtering the platelet concentrate preparation in thefilter apparatus for removing leukocyte of this invention, theleukocytes can be removed until the number of the residual leukocytes inthe recovered solution becomes less than 1×10³ leukocytes/5 units.

When leukocyte is removed using the filter apparatus for removingleukocyte of this invention while the blood transfusion is carried outon the bed side in a hospital, it is preferable to filter theleukocyte-containing solution at a rate of not less than 1 g/min butless than 20 g/min. On the other hand, when leukocyte is removed from ablood preparation for blood transfusion using the filter apparatus forremoving leukocyte of this invention in the blood center, it ispreferable to filter the leukocyte-containing solution at a rate of notless than 20 g/min but less than 100 g/min.

The filter apparatus for removing leukocyte of this invention can beused for the purpose of not only removing leukocyte, which causesvarious side effects after the transfusion, from a blood preparation forblood transfusion but also removing leukocyte in the extracorporealcirculation therapy of an autoimmune disease. The extracorporealcirculation therapy of an autoimmune disease comprises continuouslyfiltering the body fluid of a patient, which is the leukocyte-containingsolution, in the filter apparatus for removing leukocyte of thisinvention and returning the recovered solution into the body, therebyremoving leukocyte from the body fluid.

As described above, the leukocyte-removing filter material of thisinvention is very high in affinity with leukocyte, so that it ispossible to treat the leukocyte-containing solution with a goodefficiency without lowering the treatment rate.

This invention is explained in more detail below based on Examples;however, the scope of this invention should not be construed to belimited to these Examples.

EXAMPLE 1

The preparation of very fine fibers was carried out by the followingmethod. Cuprammonium rayon yarns having a fiber diameter of about 10 μm(Benberg® yarns of 40 d/45 f manufactured by Asahi Kasei Kogyo K. K.)were used as cleavable fibers and cut to a fiber length of about 3 mm.They were immersed in 3% by weight aqueous sulfuric acid solution andsubjected to acid treatment at 70° C. for 30 minutes with slowlystirring at 60 rpm. The sulfuric acid was washed away with pure waterand then 1.5 g of the fibers obtained were dispersed in 1 L of purewater and then violently stirred at 10,000 rpm for 30 minutes using ahomogenizer to prepare extremely fine fibers.

As a porous element which was the base material, there was used anonwoven fabric made of a polyester having an average fiber diameter of1.2 μm prepared by a melt-blow method and coated with a copolymercomposed of 2-hydroxyethyl methacrylate and N,N-dimethylaminoethylmethacrylate (referred to hereinafter as DM) (the DM content in thecopolymer was 3 mole %). Speaking in more detail, the above nonwovenfabric made of the polyester was immersed at 40° C. for 1 minute in a0.2% ethanolic solution of the above copolymer and thereafter theexcessive copolymer solution was removed by light squeezing, after whichthe nonwoven fabric was packed in an exclusive vessel and dried whilenitrogen was fed thereinto. The porous diameter had an average porediameter of 9.2 μm, a thickness of 0.2 mm, a bulk density of 0.2 g/cm³and a basis weight of 40 g/m². The measurement of the average porediameter was effected using PORE SIZER 9320 (Shimadzu Corp.) in apressure range of from 1 psia to 2,650 psia, and the average porediameter was determined to be a fine pore diameter corresponding to anamount of mercury pressurized of 50% obtained under the conditions thatthe amount of mercury pressurized at a mercury-pressurizing pressure of1 psia was 0% and the amount of mercury pressurized at amercury-pressurizing pressure of 650 psia was 100%. The above porouselement was cut to a true circle having a diameter of 15 cm and this wasarranged on the base of a magnetic funnel having a diameter of 15 cm,after which pure water was stored until a height of about 1 cm from thesurface of the porous element. Thereinto was gently poured 50 mL of anaqueous dispersion of the extremely fine fibers (fiber concentration:0.1 g/L) and slowly stirred. Thereafter, the water was discharged at onetime from the base of the magnetic funnel to keep the extremely finefibers on the porous element, and the fibers were dried under vacuum at40° C. for 16 hours to obtain a filter material. This operation wasrepeated twice to prepare a filter material in which extremely finefibers are kept on both surfaces of the front and back sides of theporous element.

The average fiber diameter of the fiber structure kept on the porouselement was 0.29 μm. The average fiber diameter was determined by takingan electron micrograph of the filter material obtained using a scanningtype electron microscope (S-2460N manufactured by Hitachi Ltd.),selecting extremely fine fibers at random, measuring the fiber diametersat 100 or more points and calculating the number average value thereof.Accordingly, the ratio between the average pore diameter of the porouselement and the average fiber diameter of the fiber structure became31.7 and the ratio between the average fiber diameter of the porouselement and the average fiber diameter of the fiber structure became4.1.

Moreover, the porosity of the filter material was 85%, the keepingproportion of the fiber structure to the filter material was 1.1% byweight. The measurement of porosity was as follows: The dry weight (W₁of the filter material cut to a circle of 25 mm in diameter wasmeasured, the thickness thereof was further measured using PEACOK tocalculate the volume (V). This filter material was immersed in purewater and subjected to deaeration while irradiated with an ultrasonicwave for about 30 seconds, after which the weight (W₂) of thewater-containing filter material was measured. From these values, theporosity was determined according to the calculation equation shownbelow. Incidentally, in the following equation, ρ is the density of purewater and in the present experiment, 1.0 g/cm³ was substituted therefor.

    Porosity (%)=(W.sub.2 -W.sub.1)×ρ×100/V.

The measurement of the keeping proportion of extremely fine fibers wascarried out by the method shown below. That is to say, three sheets of afilter material cut to a circle of 25 mm in diameter were immersed in 5mL of a solution prepared by dissolving 50 mg of cellulase (manufacturedby Wako Pure Chemical Industries, Ltd.) in 100 mL of a 0.1 mole/L aceticacid buffer solution (pH: 4.8) and gradually shaken at 50° C. for 24hours to decompose the extremely fine fibers into glucose which wasextracted. The decomposed and extracted glucose was subjected toquantitative determination using glucose CII-TESTWAKO (manufactured byWako Pure Chemical Industries, Ltd.) which was a glucose determiningreagent, and from the amount of glucose, the keeping proportion of theextremely fine fibers introduced into the porous element was calculated.

A laminate (2.6 g) of 7 sheets of the filter material prepared asmentioned above was packed in a vessel having an effective sectionalarea of filtering portion of 9.0 cm² (3.0 cm×3.0 cm) so that the packingdensity became 0.21 g/cm³ to prepare a filter apparatus for removingleukocyte. The total volume of the filter material was 1.26 cm³. To 400mL of blood were added 56 mL of a CPD solution (composition: 26.3 g/L ofsodium citrate, 3.27 g/L of citric acid, 23.20 g/L of glucose and 2.51g/L of sodium hydrogenphosphate dihydrate) to prepare 456 mL of wholeblood, and this whole blood was centrifuged and thereafter platelet-richplasma was removed, after which 95 mL of an MAP solution (composition:1.50 g/L of sodium citrate, 0.20 g/L of citric acid, 7.21 g/L ofglucose, 0.94 g/L of sodium hydrogenphosphate dihydrate, 4.97 g/L ofsodium chloride, 0.14 g/L of adenine and 14.57 g/l of mannitol) wasadded to prepare concentrated erythrocyte (RC-MAP). Fifty grams of theconcentrated erythrocyte (RC-MAP, hematocrit: 64%, number oferythrocytes: 3,425 cells/μL) which had been stored at 4° C. for 8 dayswas filtered through the above-mentioned filter apparatus for removingleukocyte. The temperature of the concentrated erythrocyte just beforethe starting of filtration was 10° C. The filtration of the concentratederythrocyte in the above filter apparatus was carried out at a fallingdistance of 1.0 m until the presence of the concentrated erythrocyte inthe blood bag became not confirmed, to recover the blood (the recoveredconcentrated erythrocyte is referred to hereinafter as the recoveredliquid). The average treating rate in the filtration of the concentratederythrocyte was 11.6 g/min.

The volumes of the concentrated erythrocyte before filtration (referredto hereinafter as the liquid before filtration) and the recovered liquidand the number of leukocytes were measured and the proportion of theresidual leukocyte was determined.

    Proportion of the residual leukocyte=(number of leukocytes in the recovered liquid)/(number of leukocytes in the liquid before filtration)

Incidentally, the volumes of the liquid before filtration and therecovered liquid were values obtained by dividing the respective weightsby the specific gravity of the blood preparation (1.075). The leukocyteconcentration in the liquid before filtration was measured by injectingthe liquid before filtration diluted 10 times with a Turk's reagent intoa Burker-Turk hemocytometer and counting the number of leukocytes usingan optical microscope. Also, the measurement of the leukocyteconcentration in the recovered liquid was carried out by the methodshown below. The recovered liquid was diluted to 5 times with aLEUCOPLATE solution (manufactured by SOBIODA Company). The dilutedliquid was well mixed and thereafter allowed to stand at roomtemperature for 6 to 10 minutes. This was centrifuged at 2,750×g for 6minutes and the supernatant was removed to adjust the amount of theliquid to 1.02 g. This sample liquid was well mixed and thereafterinjected into a Nageotte hemocytometer and counting the number ofleukocytes using an optical microscope, thereby determining theleukocyte concentration. From the above results, it was found that theproportion of the residual leukocyte was 10⁻².71.

COMPARATIVE EXAMPLE 1

A laminate (0.29 g) of 8 sheets of only the same porous element as suedin Example 1 (average fiber diameter: 1.2 μm, average pore diameter: 9.2μm) was packed in a vessel having an effective sectional area offiltering portion of 9.0 cm² (3.0 cm×3.0 cm) so that the packing densitybecame 0.20 g/cm³ to prepare a filter apparatus for removing leukocyte.The porosity of the above porous element was 86% and the volume thereofwas 1.44 cm³. Using this filter apparatus, 50 g of the same concentratederythrocyte liquid as in Example 1 was filtered in the same manner as inExample 1. The temperature of the concentrated erythrocyte just beforethe starting of filtration was 10° C. From the above results, it wasfound that the average treating rate was 13.2 g/min and the proportionof the residual leukocyte was 10⁻¹.18.

COMPARATIVE EXAMPLE 2

A nonwoven fabric made of polyethylene having an average fiber diameterof 0.6 μm prepared by a flash-spinning process was freeze-crushed usinga liquefied nitrogen to obtain a small fiber mass having a longerdiameter of less than 1 mm. In 5 L of a 1% by weight ethanolic Tween® 20solution were dispersed 0.1 g of the above small fiber mass and 1.5 g offibers prepared by cutting long fibers made of a polyester having anaverage fiber diameter of 7.2 μm to a 5-mm fiber length. This dispersionwas poured into a magnetic funnel, on the base of which a mesh of anopen pore diameter of 200 μm was arranged, and then the ethanol was atone time discharged to obtain a filter having a basis weight of 50 g/m².

LeukoNet® which was a leukocyte-removing filter manufactured by HEMASURECompany was disjointed and a filter material was taken out. This filtermaterial was a nonwoven fabric-like filter material made of a mixture offibers having different fiber diameters in which the average fiberdiameter of the extremely fine fibers was 0.5 μm; the average fiberdiameter of the base material was 7.8 μm; the ratio between the averagefiber diameter of the base material and the average fiber diameter ofthe extremely fine fiber was 15.6; and the porosity of the filtermaterial was 92%. As a result of observation through an electronmicroscope, the above-mentioned two kinds of filter materials weresimilar in structure and both did not form a reticulate structure. Anelectron micrograph of the latter filter material is shown in FIG. 3.Among the above two kinds of filter materials, one sheet (0.20 g) of thelatter filter material was packed in a vessel having an effectivesectional area of filtering portion of 9.0 cm³ (3.0 cm×3.0 cm) so thatthe packing density became 0.13 g/cm³ to prepare a leukocyte-removingfilter material. The total volume of the filter material was 1.53 cm³.Using this filter apparatus, 50 g of the same concentrated erythrocyteas in Example 1 was filtered in the same manner as in Example 1. Thetemperature of the concentrated erythrocyte just before the filtrationwas 10° C. From the above results, it was found that the averagetreating rate was 9.5 g/min and the proportion of the residual leukocytewas 10⁻⁰.68.

Example 1, Comparative Example 1 and Comparative Example 2 arecomparisons of the effect of introducing fibers having an average fiberdiameter of not less than 0.01 μm but less than 1.0 μm and the effect ofreticulate structure of the said fibers. Also, it is often observed inthe case of the conventional fiber-like leukocyte-removing filtermaterial that leukocytes are captured in the state that they contactwith the fibers at about 1 to 3 points; however, it is relatively oftenobserved in the case of the filter material of this invention thatleukocytes are captured in the state that they contact with the fibersat so many points as 3 or more points.

EXAMPLE 2

The above fibers prepared in the same manner as in Example 1 were keptin the same manner as in Example 1 on the same porous element as used inExample 1 to prepare a filter material in which extremely fine fiberswere kept on both surfaces on the front and back sides of the porouselement. The extremely fine fibers kept had an average fiber diameter of0.25 μm; the ratio between the average pore diameter of the porouselement and the average fiber diameter of the extremely fine fibers was36.8; the ratio between the average fiber diameter of the porous elementand the average fiber diameter of the extremely fine fibers was 4.8; theporosity of the filter material was 85% and the keeping proportion ofthe fiber structure to the filter material was 1.3% by weight. Alaminate (0.26 g) of 7 sheets of this filter material was packed in avessel having an effective sectional area of filtering portion of 9.0cm² (3.0 cm×3.0 cm) so that the packing density became 0.21 g/cm³ toprepare a filter apparatus for removing leukocyte. The total volume ofthe filter material was 1.26 cm³. Using this filter apparatus, 50 g ofconcentrated erythrocyte (RC-MAP, hematocrit: 62%, number of leukocytes:3,785 cells/μL) which had been stored at 4° C. for 7 days, was filteredin the same manner as in Example 1. The temperature of the concentratederythrocyte just before the starting of filtration was 10° C. From theabove results, it was found that the average treating rate was 10.2g/min and the proportion of the residual leukocyte was 10⁻².97.

EXAMPLE 3

The same porous element as used in Example 1 was cut to a size of 25cm×35 cm, immersed in 375 mL of a culture medium having an acetic acidbacterium concentration of 164 cells/mL and subjected in this state tostationary culture at 28° C. for 14 hours. During the stationaryculture, the porous element was turned upside down every two hours.After completion of the stationary culture, washing with a water streamwas effected to remove the acetic acid bacteria. According to theabove-mentioned production process, there was obtained a filter materialin which a reticulate structure composed of cellulose fibers produced bythe acetic acid bacterium having an average fiber diameter of 0.02 μmwere kept on the surfaces of the front and back sides of the porouselement. As the acetic acid bacterium, there was used Acetobacterxylinum IFO13693). The composition of the culture medium was 2% of grapesugar, 0.5% of polypeptone, 0.5% of yeast extract, 0.27% of sodiumhydrogenphosphate anhydride and 0.115% of citric acid monohydrate. As amethod of determining the number of bacterial cells in the culturemedium, a colony counting method was used. That is to say, a suspensionof the acetic acid bacterium in the culture medium was diluted and agiven amount thereof was sampled. This was mixed with a culture mediumcontaining 0.75% of agar, then poured onto a petri dish and cooled for ashort period of time to be solidified. Thereto was further added a givenamount of a culture medium containing 0.75% of agar, and the culturingwas continued for at least 4 days and the number of colonies formed outof acetic acid bactera's cells was counted, thereby determining thenumber of bacterial cells. As a result of observation through anelectron microscope, this filter material formed a reticulate structure.The average fiber diameter of the fiber structure was 0.02 μm, the ratiobetween the average pore diameter of the porous element to the averagefiber diameter of the fiber structure was 460, the ratio between theaverage fiber diameter of the porous element and the average fiberdiameter of the fiber structure was 60, the porosity of the filtermaterial was 85% and the keeping proportion of the fiber structure tothe filter material was 0.05% by weight.

0.26 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm×3.0 cm)so that the packing density became 0.21 g/cm³ to prepare a filterapparatus for removing leukocyte. The total volume of the filtermaterial was 1.26 cm³. Using this filter apparatus, 50 g of the sameconcentrated erythrocyte as in Example 2 (RC-MAP, hematocrit: 62%,number of leukocytes: 3,785 cells/μL) was filtered in the same manner asin Example 1. The temperature of the concentrated erythrocyte justbefore the starting of filtration was 10° C. From the above results, itwas found that the average treating rate was 12.4 g/min and theproportion of the residual leukocyte was 10⁻².80.

EXAMPLE 4

To a high pressure liquid treatment was subjected a filter material inwhich the extremely fine fibers were kept on both surfaces of the frontand back sides of a porous element which filter material had beenobtained by subjecting to the same operation as in Example 1 the sameporous element as used in Example 1 and extremely fine fibers preparedby cutting cuprammonium rayon yarn (Benberg® yarn of 40 d/45 fmanufactured by Asahi Kasei Kogyo K. K.) having a fiber diameter ofabout 10 μm so that the fiber length became about 0.8 mm and subjectingthe fibers to the same operation as in Example 1. That is to say, theabove filter material was subjected to columnar stream treatment (15kg/cm²) under the conditions that the nozzle diameter was 0.2 mm, thenozzle pitch was 5 mm, the number of nozzle lines was 18, the distancebetween web and nozzle was 30 mm, the number of revolutions of nozzleheader was 150 rpm and the moving speed of filter material was 5 m/minto prepare a filter material. As a result of observation through anelectron microscope, this filter material formed a reticulate structure.The average fiber diameter of the extremely fine fibers was 0.23 μm, theratio between the average pore diameter of the porous element and theaverage fiber diameter of the extremely fine fibers was 40.0, the ratiobetween the average fiber diameter of the porous element and the averagefiber diameter of the extremely fine fibers was 5.2, the porosity of thefilter material was 82% and the keeping proportion of the fiberstructure to the filter material was 10.3% by weight.

0.33 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm×3.0 cm)so that the packing density became 0.26 g/cm³ to prepare a filterapparatus for removing leukocyte. The total volume of the filtermaterial was 1.26 cm³. Using this filter apparatus, the sameconcentrated erythrocyte as in Example 2 (RC-MAP, hematocrit: 62%,number of leukocytes: 3,785 cells/μL) was filtered in the same manner asin Example 1. The temperature of the concentrated erythrocyte justbefore the starting of filtration was 10° C. From the above results, itwas found that the average treating speed was 6.7 g/min and theproportion of the residual leukocyte was 10⁻³.10.

COMPARATIVE EXAMPLE 3

The same porous element as used in Example 1 was cut to a size of 25cm×35 cm, immersed in 375 mL of a culture medium having an acetic acidbacterium concentration of 164 cells/mL and subjected in this state tostationary culture at 28° C. for 2 hours. After completion of thestationary culture, washing with a water stream was effected to removethe acetic acid bacterium. By the above-mentioned production process,there was obtained a filter material in which a reticulate structurecomposed of cellulose fibers produced by the acetic acid bacteriumhaving an average fiber diameter of 0.02 μm were kept on the surface ofone side of the porous element. The acetic acid bacterium used and thecomposition of the culture medium were the same as in Example 3. Theaverage fiber diameter of the extremely fine fiber structure was 0.02μm, the ratio between the average pore diameter of the porous element tothe average fiber diameter of the extremely fine fiber structure was460, the ratio between the average fiber diameter of the porous elementand the average fiber diameter of the extremely fine fiber structure was60, the porosity of the filter material was 85% and the keepingproportion of the extremely fine fiber structure to the filter materialwas 0.005% by weight.

0.26 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm×3.0 cm)so that the packing density became 0.21 g/cm³ to prepare a filterapparatus for removing leukocyte. The volume of the filter material was1.26 cm³. Using this filter apparatus, 50 g of the same concentratederythrocyte as in Example 2 (RC-MAP, hematocrit: 62%, number ofleukocytes: 3,785 cells/μL) was filtered in the same manner as inExample 1. The temperature of the concentrated erythrocyte just beforethe staring of filtration was 10° C. From the above results, it wasfound that the average treating rate was 10.2 g/min and the proportionof the residual leukocyte was 10⁻¹.67.

COMPARATIVE EXAMPLE 4

Extremely fine fibers prepared in the same manner as in Example 1 andthe same porous element as used in Example 1 were subjected to the sameoperation as in Example 1 to obtain a filter material in which theextremely fine fibers were kept on both surfaces of the front and backsides of the porous element. Such a filter material was prepared thatthe average fiber diameter of the extremely fine fibers was 0.25 μm, theratio between the average pore diameter of the porous element and theaverage fiber diameter of the extremely fine fiber structure was 36.8,the ratio between the average fiber diameter of the porous element andthe average fiber diameter of the extremely fine structure was 4.8, theporosity of the filter material was 48% and the keeping proportion ofthe fiber structure to the filter material was 59% by weight.

0.91 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm×3.0 cm)so that the packing density became 0.72 g/cm³ to prepare a filterapparatus for removing leukocyte. The total volume of the filtermaterial was 1.26 cm³. Using this filter apparatus, 50 g of concentratederythrocyte (RC-MAP, hematocrit: 62%, number of leukocytes: 3,785cells/μL) was filtered in the same manner as in Example 1. However, thefilter material caused clogging soon and the concentrated erythrocytedid not flow at all. The temperature of the concentrated erythrocytejust before the starting of filtration was 10° C.

COMPARATIVE EXAMPLE 5

Cuprammonium rayon yarn (Benberg® yarn of 40 d/45 f manufactured byAsahi Kasei Kogyo K. K.) having a fiber diameter of about 10 μm was cutso that the fiber length became about 5 mm and extremely fine fiberswere prepared according to the operation of Example 1. The treatment ina homogenizer was effected at 10,000 rpm for 5 minutes. Using theextremely fine fibers prepared, a nonwoven fabric made of a polyesterhaving an average fiber diameter of 1.2 μm and an average pore diameterof 1.6 μm prepared by a melt-blow method, as a porous element, wassubjected to coating treatment using a 0.2% ethanolic solution of acopolymer consisting of 2-hydroxyethyl methacrylate andN,N-dimethylaminoethyl methacrylate (the DM content in the copolymer was3 mole %) in the same manner as in Example 1, and then toheat-compression at 110° C. Using this porous element, a filter materialin which the extremely fine fibers were kept on both surfaces of thefront and back sides of the porous element was obtained in the samemanner as in Example 1. The fiber structure kept on the porous elementformed a reticulate structure. Such a filter material was prepared thatthe average fiber diameter of the fiber structure was 0.93 μm, the ratiobetween the average pore diameter of the porous element and the averagefiber diameter of the fiber structure was 1.7, the ratio between theaverage fiber diameter of the porous element and the average fiberdiameter of the fiber structure was 1.3, the porosity of the filtermaterial was 55% and the keeping proportion of the fiber structure tothe filter material was 1.3% by weight.

0.78 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm ×3.0cm) so that the packing density became 0.62 g/cm³ to prepare a filterapparatus for removing leukocyte. The total volume of the filtermaterial was 1.26 cm³. Using this filter apparatus, 50 g of concentratederythrocyte (RC-MAP, hematocrit: 62%, number of leukocytes: 3,785cells/μL) was filtered in the same manner as in Example 1. However, thefilter material caused clogging soon and the concentrated erythrocytedid not flow at all. The temperature of the concentrated erythrocytejust before the starting of filtration was 10° C.

COMPARATIVE EXAMPLE 6

A porous element prepared by subjecting a spunbonded nonwoven fabricmade of a polyester having an average fiber diameter of 25 μm and anaverage pore diameter of 85 μm to coating treatment with a 0.2%ethanolic solution of a copolymer consisting of 2-hydroxyethylmethacrylate and N,N-dimethylaminoethyl methacrylate (DM) (the DMcontent in the copolymer was 3 mole %) in the same manner as in Example1, was cut to a size of 25 cm×35 cm, immersed in 375 mL of a culturemedium having an acetic acid bacterium concentration of 112 cells/mL,and subjected in this state to stationary culture at 28° C. for 10hours. During the stationary culture, the porous element was turnedupside down every 2 hours. After completion of the stationary culture,washing with a water stream was effected to remove the acetic acidbacterium. According to the above production process, there was obtaineda filter material in which a fiber structure composed of cellulosefibers having an average fiber diameter of 0.02 μm produced by theacetic acid bacterium was kept on the surfaces of the front and backsides of the porous element. The acetic acid bacterium used and thecomposition of the culture medium used were the same as in Example 3.The average fiber diameter of the fiber structure was 0.02 μm, the ratiobetween the average pore diameter of the porous element and the averagefiber diameter of the fiber structure was 4,250, the ratio between theaverage fiber diameter of the porous element and the average fiberdiameter of the fiber structure was 1,250, the porosity of the porouselement was 85% and the keeping proportion of the fiber structure to thefilter material was 0.01% by weight.

0.26 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm×3.0 cm)so that the packing density became 0.21 g/cm³ to prepare a filterapparatus for removing leukocyte. The total volume of the filtermaterial was 1.26 cm³. Using this filter apparatus, in the same manneras in Example 1, 50 g of the same concentrated erythrocyte as in Example2 (RC-MAP, hematocrit: 62%, number of leukocytes: 3,785 cells/μL) wasfiltered. The temperature of the concentrated erythrocyte just beforethe starting of filtration was 10° C. From the above results, it wasfound that the average treating rate was 25.2 g/min and the proportionof the residual leukocyte was 10⁻⁰.08.

Examples 2 to 4 and Comparative Examples 3 to 6 are comparisons of thekeeping proportion of fibers having an average fiber diameter of notless than 0.01 μm but less than 1.0 μm to the filter material, the ratiobetween the average pore diameter of the porous element and the averagefiber diameter of the fiber structure, or the ratio between the averagefiber diameter of the porous element and the average fiber diameter ofthe fiber structure.

EXAMPLE 5

Extremely fine fibers prepared in the same manner as in Example 1 and acontinuous porous element made of a polyurethane having an average porediameter of 7.6 μm as the porous element were subjected to the sameoperation as in Example 1 to obtain a filter material in which theextremely fine fibers were kept on both surfaces on the front and backsides of the porous element. The extremely fine fibers had an averagefiber diameter of 0.25 μm, the ratio between the average pore diameterof the porous element and the average fiber diameter of the fiberstructure was 30.4, the porosity of the filter material was 87% and thekeeping proportion of the fiber structure to the filter material was1.3% by weight.

0.23 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm×3.0 cm)so that the packing density became 0.21 g/cm³ to prepare a filterapparatus for removing leukocyte. The total volume of the filtermaterial was 1.08 cm³. Using this filter apparatus, 50 g of concentratederythrocyte (RC-MAP, hematocrit: 62%, number of leukocytes: 4,125cells/μL) which had been stored at 4° C. for 8 days was filtered in thesame manner as in Example 1. The temperature of the concentratederythrocyte just before the starting of filtration was 10° C. From theabove results, it was found that the average treating rate was 14.6g/min and the proportion of the residual leukocyte was 10⁻².83.

EXAMPLE 6

The same porous element as used in Example 1 was cut to a size of 25cm×35 cm, immersed in 375 mL of a culture medium having an acetic acidbacterium concentration of 183 cells/mL and subjected in this state tostationary culture at 28° C. for 14 hours. During the stationaryculture, the porous element was turned upside down every two hours.After completion of the stationary culture, washing with a water streamwas effected to remove the acetic acid bacterium. According to theabove-mentioned production process, there was obtained a filter materialin which a reticulate fiber structure composed of cellulose fibersproduced by the acetic acid bacterium having an average fiber diameterof 0.02 μm were kept on the surfaces on the front and back sides of theporous element. The acetic acid bacterium used and the composition ofthe culture medium used were the same as in Example 3. The average fiberdiameter of the fiber structure was 0.02 μm, the ratio between theaverage pore diameter of the porous element and the average fiberdiameter of the fiber structure was 460, the ratio between the averagefiber diameter of the porous element and the average fiber diameter ofthe fiber structure was 60, the porosity of the filter material was 85%and the keeping proportion of the fiber structure to the filter materialwas 0.06% by weight.

0.30 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm×3.0 cm)so that the packing density became 0.21 g/cm³ to prepare a filterapparatus for removing leukocyte. The total volume of the filtermaterial was 1.44 cm³. Using this filter apparatus, 50 g of the sameconcentrated erythrocyte as in Example 5 (RC-MAP, hematocrit: 62%,number of leukocytes: 4,125 cells/μL) was filtered in the same manner asin Example 1. The temperature of the concentrated erythrocyte justbefore the starting of filtration was 10° C. From the above results, itwas found that the average treating rate was 11.2 g/min and theproportion of the residual leukocyte was 10⁻².92.

COMPARATIVE EXAMPLE 7

The same porous element as used in Example 1 was cut to a size of 25cm×35 cm, immersed in 500 mL of a culture medium having an acetic acidbacterium concentration of 465 cells/mL and subjected in this state tostationary culture at 28° C. for 10 hours. After completion of thestationary culture, washing with a water stream was effected to removethe acetic acid bacterium. According to the above-mentioned productionprocess, there was obtained a filter material which was a composite ofthe porous element with the bacterial cellulose membrane. The aceticacid bacterium used and the composition of the culture medium used werethe same as in Example 3. The average fiber diameter of the fibersforming the bacterial cellulose membrane was 0.02 μm, the ratio betweenthe average pore diameter of the porous element to the average fiberdiameter of the fiber structure was 460, the ratio between the averagefiber diameter of the porous element and the average fiber diameter ofthe fiber structure was 60, the porosity of the filter material was 85%and the keeping proportion of the fiber structure to the filter materialwas 50.3% by weight.

0.67 g of this filter material was packed in a vessel having aneffective sectional area of filtering portion of 9.0 cm² (3.0 cm×3.0 cm)so that the packing density became 0.40 g/cm³ to prepare a filterapparatus for removing leukocyte. The total volume of the filtermaterial was 1.68 cm³. Using this filter apparatus, 50 g of the sameconcentrated erythrocyte as in Example 5 (RC-MAP, hematocrit: 62%,number of leukocytes: 4,125 cells/μL) was filtered in the same manner asin Example 1. However, the filter material caused clogging soon and theconcentrated erythrocyte did not flow at all. The temperature of theconcentrated erythrocyte just before the starting of filtration was 10°C.

EXAMPLE 7

To the same operation as in Example 1 were subjected extremely finefibers prepared in the same manner as in Example 1 and a nonwoven fabricmade of a polyester having an average fiber diameter of 1.2 μm and anaverage pore diameter of 9.2 μm prepared by a melt-blow method to obtaina filter material in which the extremely fine fibers were kept on bothsurfaces on the front and back sides of a porous element. The averagefiber diameter of the extremely fine fibers was 0.29 μm, the ratiobetween the average pore diameter of the porous element and the averagefiber diameter of the fiber structure was 31.7, the ratio between theaverage fiber diameter of the porous element and the average fiberdiameter of the fiber structure was 4.1, the porosity of the filtermaterial was 85% and the keeping proportion of the fiber structure tothe filter material was 1.2% by weight.

On the upper stream side of 1.8 g of this filter material were arranged0.63 g of a nonwoven fabric made of a polyester having an average fiberdiameter of 19 μm and a basis weight of 70 g/m², 0.27 g of a nonwovenfabric made of a polyester having an average fiber diameter of 12 μm anda basis weight of 30 g/m² and 0.59 g of a nonwoven fabric made of apolyester having an average fiber diameter of 1.7 μm and a basis weightof 66 g/m², and they were packed in a vessel having an effectivesectional area of filtering portion of 45 cm² (6.7 cm×6.7 cm) so thatthe packing density became 0.23 g/cm³. Into this vessel was poured at aflow rate of 80 g/min a 0.2% ethanolic solution of a copolymerconsisting of 2-hydroxyethyl methacrylate and N,N-dimethylaminoethylmethacrylate (DM) (the DM content in the copolymer was 3 mole %) whilethe ethanolic solution was maintained at 40° C., and then recycled for1.5 hours, after which nitrogen was introduced into the vessel at a flowrate of 1.5 L/min to remove the excessive coating solution. Vacuumdrying was further effected at 60° C. for 16 hours to prepare a filterapparatus for removing leukocyte.

Using this filter apparatus, 515 g of CPD-added fresh human whole blood(hematocrit: 39%, number of leukocytes: 4,865 cells/μL) was filtered.The temperature of the CPD-added fresh human whole blood just before thestarting of filtration was 25° C. When the filtration was started, thefilter apparatus was connected to a blood bag containing the CPD-addedfresh human whole blood through the blood circuit, and thereafter, apressure of 100 mmHg was applied to the blood bag using a pressuringcuff to forcibly fill the filter apparatus with the CPD-added freshhuman whole blood. After the filter apparatus had been filled with theCPD-added fresh human whole blood as mentioned above, the CPD-addedfresh human whole blood was treated at a falling distance of 0.7 m andthe filtration was carried out until the presence of the CPD-added freshhuman whole blood in the blood bag was not been confirmed, and thefiltered blood was recovered. From the above results, it was found thatthe average treating rate was 29.6 g/min, the proportion of the residualleukocyte was 10⁻³.99 and the recovery of erythrocyte was 93.8%.

COMPARATIVE EXAMPLE 8

In Example 7, 5.78 g of a nonwoven fabric made of a polyester having anaverage fiber diameter of 1.2 μm and an average pore diameter of 9.3 μmprepared by a melt-blow method was packed in place of the filtermaterial of this invention and subjected to the same coating treatmentas in Example 7 to prepare a filter apparatus. Incidentally, the packingdensity was adjusted to 0.26 g/cm³.

Using this filter apparatus, the same CPD-added fresh human whole bloodas in Example 7 was treated in the same manner as in Example 7. As aresult, it was found that the average treating rate was 24.8 g/min, theproportion of the residual leukocyte was 10⁻³.91 and the recovery oferythrocyte was 89.6%.

Though the amount of the filter material in the filter apparatus inExample 7 was about 1/3 of the amount of the main filter material(filter material having an average fiber diameter of 1.2 μm) in thefilter apparatus in Comparative Example 8, it can be seen that theleukocyte-removing performance and the average treating rate were atleast equivalent and the loss of erythrocyte was reduced about 40%.

EXAMPLE 8

On the upper stream side of 1.3 g of the same filter material of thisinvention as in Example 7 were arranged 1.35 g of a nonwoven fabric madeof a polyester having an average fiber diameter of 33 μm and a basisweight of 50 g/m², 0.81 g of a nonwoven fabric made of a polyesterhaving an average fiber diameter of 12 μm and a basis weight of 30 g/m²and 0.59 g of a nonwoven fabric made of a polyester having an averagefiber diameter of 1.7 μm and a basis weight of 66 g/m², and they werepacked in a vessel having an effective sectional area of filteringportion of 45 cm² (6.7 cm×6.7 cm) so that the packing density became0.22 g/cm³ and then subjected to the same coating treatment as inExample 7 to prepare a filter apparatus.

Using this filter apparatus, 325 g of concentrated erythrocyte (RC-MAP,hematocrit: 64%, number of leukocytes: 5,260 cells/μL) which had beenstored at 4° C. for 10 days was filtered in the same manner as inExample 7 at a falling distance of 1.0 m. The temperature of theconcentrated erythrocyte just before the starting of filtration was 12°C. From the above results, it was found that the average treating ratewas 17.6 g/min, the proportion of the residual leukocyte was 10⁻⁴.02 andthe recovery of erythrocyte was 94.3%.

COMPARATIVE EXAMPLE 9

In Example 8, a nonwoven fabric made of a polyester having an averagefiber diameter of 1.2 μm and an average pore diameter of 9.3 μm preparedby a melt-blow method was packed in place of the filter material of thisinvention and subjected to the same coating treatment as in Example 7 toprepare a filter apparatus. Incidentally, the packing density wasadjusted to 0.22 g/cm³.

Using this filter apparatus, 325 g of the same concentrated erythrocyteas in Example 8 (RC-MAP, hematocrit: 64%, number of leukocytes: 5,260cells/μL) was filtered in the same manner as in Example 8 at a fallingdistance of 1.0 m. As a result, it was found that the average treatingrate was 19.5 g/min, the proportion of the residual leukocyte was10⁻³.94, and the recovery of erythrocyte was 89.2%.

Though the amount of the filter material in the filter apparatus inExample 8 was about 1/3 of that of the main filter material (filtermaterial having an average fiber diameter of 1.2 μm) in the filterapparatus of Comparative Example 9, it can be seen that theleukocyte-removing performance and the average treating rate in thefilter apparatus of Example 8 were at least equivalent and in addition,the loss of erythrocyte was reduced about 50%.

EXAMPLE 9

On the upper stream side of 0.32 g of the same filter material of thisinvention as in Example 7 were arranged 0.13 g of a nonwoven fabric madeof a polyester having an average fiber diameter of 19 μm and a basisweight of 70 g/m² and 0.11 g of a nonwoven fabric made of a polyesterhaving an average fiber diameter of 2.3 μm and a basis weight of 60g/m², and they were packed in a vessel having an effective sectionalarea of filtering portion of 9 cm² (3.0 cm×3.0 cm) so that the packingdensity became 0.21 g/cm³. Into this vessel was poured at a flow rate of80 g/min a 1.0% ethanolic solution of a copolymer composed of2-hydroxyethyl methacrylate and N,N-dimethylaminoethyl methacrylate (DM)(the DM content in the copolymer was 3 mole %) while the ethanolicsolution was maintained at 40° C., and recycled for 1.5 minutes, afterwhich nitrogen was introduced at a flow rate of 1.5 L/min into thevessel to remove the excessive coating solution. In addition, byeffecting vacuum drying at 40° C. for 16 hours, a filter apparatus forremoving leukocyte was prepared.

Using this filter apparatus, 400 g of platelet concentrate (number ofplatelets: 9.9×10⁵ cells/μL, number of leukocytes: 1,075 cells/μL) whichhad been stored at room temperature for 4 days with gentle shaking wasfiltered. The temperature of the platelet concentrate just before thestarting of filtration was 23° C. The platelet concentrate was treatedat a falling distance of 1.0 m and the filtration was effected until thepresence of the platelet concentrate in the blood bag was not confirmed,and the filtered blood was recovered. The leukocyte concentration of theliquid before filtration was determined by injecting the liquid beforefiltration diluted 10 times with a Turk's reagent into a Burker-Turktype hemocytometer and counting the number of leukocytes through anoptical microscope to determine the leukocyte concentration. Theleukocyte concentration in the recovered liquid was determined byconcentrating the recovered liquid to 10 times or 20 times by acentrifugal operation (800 G×10 minutes), dyeing the leukocytes with anacridine orange solution and then counting them using a Neubauerhemocytometer. The platelet concentration was measured by an automatichemocytometer Sysmex K-4500 (manufactured by Toa Iyo Denshi K. K.). Fromthe above results, it was found that the average treating rate was 27.3g/min, the proportion of the residual leukocyte was 10⁻³.73 and therecovery of platelet was 93.7%.

COMPARATIVE EXAMPLE 10

In Example 9, a nonwoven fabric made of a polyester having an averagefiber diameter of 1.2 μm and an average pore diameter of 9.3 μm preparedby a melt-blow method was packed in place of the filter material of thisinvention, and subjected to the same coating treatment as in Example 9to prepare a filter apparatus. Incidentally, the packing density wasadjusted to 0.23 g/cm³.

Using this filter apparatus, the same platelet concentrate as in Example9 was treated in the same manner as in Example 9. As a result, it wasfound that the average treating rate was 30.1 g/min, the proportion ofthe residual leukocyte was 10⁻³.38 and the recovery of platelet was85.4%.

Though the amount of the main filter material in the filter apparatus inExample 9 was about 1/3 of the amount of the main filter material(filter material having an average fiber diameter of less than 1.2 μm)in the filter apparatus in Comparative Example 10, it can be seen thatthe leukocyte-removing performance and the average treating rate in thefilter apparatus in Example 9 were at least equivalent, and in addition,the loss of the platelet was reduced about 55%.

EXAMPLE 10

Extremely fine fibers prepared in the same manner as in Example 1 and anonwoven fabric made of a polyester having an average fiber diameter of1.2 μm and an average pore diameter of 9.2 μm prepared by a melt-blowmethod were subjected to the same operation as in Example 1 to prepare afilter material kept on both surfaces on the front and back sides of theporous element. The average fiber diameter of the extremely fine fiberswas 0.19 μm, the ratio between the average pore diameter of the porouselement and the average fiber diameter of the fiber structure was 48.4,the ratio between the average fiber diameter of the porous element andthe average fiber diameter of the fiber structure was 6.3, the porosityof the filter material was 85% and the keeping proportion of the fiberstructure to the filter material was 1.4% by weight.

On the upper stream side of 3.96 g of this filter material were arranged1.35 g of a nonwoven fabric made of a polyester having an average fiberdiameter of 33 μm and a basis weight of 50 g/m², 0.81 g of a nonwovenfabric made of a polyester having an average fiber diameter of 12 μm anda basis weight of 30 g/m² and 0.59 g of a nonwoven fabric made of apolyester having an average fiber diameter of 1.7 μm and a basis weightof 66 g/m², and they were packed in a vessel having an effectivesectional area of filtering portion of 45 cm² (6.7 cm×6.7 cm) so thatthe packing density became 0.22 g/cm³. Subsequently, by applying thesame coating treatment as in Example 7, a filter apparatus for removingleukocyte was prepared.

Using this filter apparatus, 325 g of concentrated erythrocyte (RC-MAP,hematocrit: 63%, number of leukocytes: 4,935 cells/μL) which had beenstored at 4° C. for 7 days, was filtered. The temperature of theconcentrated erythrocyte just before the starting of filtration was 12°C. When the filtration was started, the filter apparatus was connectedto a blood bag containing the concentrated erythrocyte through the bloodcircuit, and thereafter, a pressure of 100 mmHg was applied to the bloodbag using a pressuring cuff to forcibly fill the filter apparatus withthe concentrated erythrocyte. After the filter apparatus had been filledwith the concentrated erythrocyte as mentioned above, the concentratederythrocyte was treated at a falling distance of 1.0 m and filtrationwas effected until the presence of the concentrated erythrocyte in theblood bag was not confirmed, and the filtered blood was recovered. Fromthe above results, it was found that the average treating rate was 16.6g/min and the proportion of the residual leukocyte was 10⁻⁵.99 or less.

COMPARATIVE EXAMPLE 11

In Example 10, a nonwoven fabric made of a polyester having an averagefiber diameter of 1.2 μm and an average pore diameter of 9.2 μm preparedby a melt-blow method was packed in place of the filter material of thisinvention and subjected to the same coating treatment as in Example 10to prepare a filter apparatus. Incidentally, the packing density wasadjusted to 0.22 g/cm³. Using this filter apparatus, 325 g of the sameconcentrated erythrocyte as in Example 10 (RC-MAP, hematocrit: 63%,number of leukocytes: 4,935 cells/μL) was filtered in the same manner asin Example 10 at a falling distance of 1.0 m. As a result, it was foundthat the average treating rate was 15.8 g/min and the proportion of theresidual leukocyte was 10⁻³.98.

Though the amounts of the filter materials in the filter apparatus inExample 10 and Comparative Example 11 were the same, it can be seen thatin the case of the filter apparatus in Example 10, theleukocyte-removing performance was extremely high as compared with thefilter apparatus in Comparative Example 11.

EXAMPLE 11

On the upper stream side of 1.3 g of the same filter material of thisinvention as in Example 10 were arranged 1.35 g of a nonwoven fabricmade of a polyester having an average fiber diameter of 33 μm and abasis weight of 50 g/m², 0.81 g of a nonwoven fabric made of a polyesterhaving an average fiber diameter of 12 μm and a basis weight of 30 g/m²and 0.59 g of a nonwoven fabric made of a polyester having an averagefiber diameter of 1.7 μm and a basis weight of 66 g/m², and they werepacked in a vessel having an effective sectional area of filteringportion of 45 cm² (6.7 cm×6.7 cm) so that the packing density became0.22 g/cm³ and then subjected to the same coating treatment as inExample 10 to prepare a filter apparatus.

Using this filter apparatus, 325 g of concentrated erythrocyte (RC-MAP,hematocrit: 62%, number of leukocytes: 6,335 cells/μL) which had beenstored at 4° C. for 9 days was filtered in the same manner as in Example10 at a falling distance of 1.0 m at an average treating rate adjustedto 5.6 g/min. The temperature of the concentrated erythrocyte justbefore the starting of filtration was 12° C. From the above results, itwas found that the proportion of the residual leukocyte was 10⁻⁴.10 andthe recovery of erythrocyte was 94.6%.

EXAMPLE 12

Using the same filter apparatus as in Example 11, the same concentratederythrocyte as in Example 11 (RC-MAP, hematocrit: 62%, number ofleukocytes: 6,335 cells/μL) was treated in the same manner as in Example11 at an average treating rate of 19.8 g/min. As a result, it was foundthat the proportion of the residual leukocyte was 10⁻³.93 and therecovery of erythrocyte was 93.9%.

EXAMPLE 13

On the upper stream side of 1.3 g of the same filter material of thisinvention as in Example 3 were arranged 1.35 g of a nonwoven fabric madeof a polyester having an average fiber diameter of 33 μm and a basisweight of 50 g/m², 0.81 g of a nonwoven fabric made of a polyesterhaving an average fiber diameter of 12 μm and a basis weight of 30 g/m²and 0.59 g of a nonwoven fabric made of a polyester having an averagefiber diameter of 1.7 μm and a basis weight of 66 g/m², and they werepacked in a vessel having an effective sectional area of filteringportion of 45 cm² (6.7 cm×6.7 cm) so that the packing density became0.22 g/cm³ and then subjected to the same coating treatment as inExample 10 to prepare a filter apparatus.

Using this filter apparatus, 325 g of concentrated erythrocyte (RC-MAP,hematocrit: 64%, number of leukocytes: 3,387 cells/μL) which had beenstored at 4° C. for 10 days was filtered in the same manner as inExample 10 at a falling distance of 1.0 m. The temperature of theconcentrated erythrocyte just before the starting of filtration was 12°C. From the above results, it was found that the average treating ratewas 24.4 g/min, the proportion of the residual leukocyte was 10⁻³.78 andthe recovery of erythrocyte was 95.1%.

EXAMPLE 14

The same porous element as used in Example 1 was cut to a size of 25cm×35 cm, immersed in 375 mL of a culture medium having an acetic acidbacterium concentration of 498 cells/mL and subjected in this state tostationary culture at 28° C. for 14 hours. During the stationaryculture, the porous element was turned upside down every two hours.After completion of the stationary culture, washing with a water streamwas effected to remove the acetic acid bacterium. According to theabove-mentioned production process, there was obtained a filter materialin which a reticulate structure composed of cellulose fibers produced bythe acetic acid bacterium having an average fiber diameter of 0.02 μmwere kept on the surfaces on the front and back sides of the porouselement. The acetic acid bacterium used and the composition of theculture medium used were the same as in Example 3. The average fiberdiameter of the fiber structure was 0.02 μm, the ratio between theaverage pore diameter of the porous element and the average fiberdiameter of the fiber structure was 460, the ratio between the averagefiber diameter of the porous element and the average fiber diameter ofthe fiber structure was 60, the porosity of the filter material was 85%and the keeping proportion of the fiber structure to the filter materialwas 0.12% by weight.

On the upper stream side of 1.3 g of this filter material were arranged1.35 g of a nonwoven fabric made of a polyester having an average fiberdiameter of 33 μm and a basis weight of 50 g/cm², 0.81 g of a nonwovenfabric made of a polyester having an average fiber diameter of 12 μm anda basis weight of 30 g/cm² and 0.59 g of a nonwoven fabric made of apolyester having an average fiber diameter of 1.7 μm and a basis weightof 66 g/cm² and they were packed in a vessel having an effectivesectional area of filtering portion of 45 cm² (6.7 cm×6.7 cm) so thatthe packing density became 0.22 g/cm³, and thereafter, subjected to thesame coating treatment as in Example 10, to prepare a filter apparatus.Using this filter apparatus, 325 g of the same concentrated erythrocyteas in Example 13 (RC-MAP, hematocrit: 64%, number of leukocytes: 3,387cells/μL) was filtered in the same manner as in Example 10 at a fallingdistance of 1.0 m. The temperature of the concentrated erythrocyte justbefore the starting of filtration was 12° C. From the above results, itwas found that the average treating rate was 14.8 g/min, the proportionof the residual leukocyte was 10⁻⁴.24, and the recovery of erythrocytewas 94.2%.

INDUSTRIAL APPLICABILITY

The leukocyte-removing filter material of this invention is useful as afilter material for use in transfusion of blood components because itcan remove leukocyte which becomes a cause for side effects with a highefficiency while maintaining a high recovery of useful blood components.

We claim:
 1. A leukocyte-removing filter material which is composed of aporous element having an average pore diameter of not less than 1.0 μmbut less than 100 μm and a fiber structure having an average fiberdiameter of not less than 0.01 μm but less than 1.0 μm kept on theporous element, wherein the porosity of the filter material is not lessthan 50% but less than 95%, the keeping proportion of the fiberstructure to the filter material is not less than 0.01% by weight butless than 30% by weight, and the ratio between the average pore diameterof the porous element and the average fiber diameter of the fiberstructure is not less than 2 but less than 2,000 and the fiber structureforms a reticulate structure.
 2. The leukocyte-removing filter materialaccording to claim 1, wherein the ratio of the average pore diameter ofthe porous element to the average fiber diameter of the fiber structureis not less than 10 but less than 1,800.
 3. The leukocyte-removingfilter material according to claim 1, wherein the keeping proportion ofthe fiber structure to the filter material is not less than 0.03% byweight but less than 10% by weight.
 4. The leukocyte-removing filtermaterial according to claim 1, wherein each of the fibers constructingthe fiber structure is a single fiber.
 5. The leukocyte-removing filtermaterial according to claim 1, wherein the average fiber diameter of thefiber structure is not less than 0.01 μm but less than 0.8 μm.
 6. Theleukocyte-removing filter material according to claim 1, wherein thefiber structure is kept on the whole of the porous element.
 7. Theleukocyte-removing filter material according to claim 6, wherein thefiber structure is substantially uniformly kept substantially on thewhole of the porous element.
 8. The leukocyte-removing filter materialaccording to claim 1, wherein the fiber structure is kept on the surfaceof one side of the porous element.
 9. The leukocyte-removing filtermaterial according to claim 8, wherein the fiber structure issubstantially uniformly kept on the surface.
 10. The leukocyte-removingfilter material according to claim 1, wherein the fiber structure iskept on the surfaces on both sides of the porous element.
 11. Theleukocyte-removing filter material according to claim 10, wherein thefiber structure is substantially uniformly kept on the surfaces.
 12. Theleukocyte-removing filter material according to claim 1, wherein theporous element is a fiber congregation.
 13. The leukocyte-removingfilter material according to claim 12, wherein the ratio of the averagefiber diameter of the fiber congregation to the average fiber diameterof the fiber structure is not less than 10 but less than 1,000.
 14. Theleukocyte-removing filter material according to claim 13, wherein thefiber congregation is a nonwoven fabric.
 15. The leukocyte-removingfilter material according to claim 13, wherein the fiber congregation isof long fibers.
 16. The leukocyte-removing filter material according toclaim 1, wherein the porous element is a spongy interconnected porousmaterial.
 17. The leukocyte-removing filter material according to claim1, wherein the thickness of the filter material in the flow direction isnot less than 0.1 mm but less than 30 mm.
 18. The leukocyte-removingfilter material according to claim 17, wherein the thickness of thefilter material in the flow direction is not less than 0.1 mm but lessthan 15 mm.
 19. The leukocyte-removing filter material according toclaim 1, wherein the porous element and/or the fiber structure issurface-modified.
 20. The leukocyte-removing filter material accordingto claim 19, wherein the surface of the porous element and/or the fiberstructure is coated with a high polymer material.
 21. Theleukocyte-removing filter material according to claim 20, wherein thesurface of the porous element and/or the fiber structure is coated witha high polymer material having a nonionic, hydrophilic group.
 22. Theleukocyte-removing filter material according to claim 20 or 21, whereinthe high polymer material is a copolymer comprising a polymerizablemonomer having a basic nitrogen-containing functional group in an amountof 0.1 to 20% as a monomer unit.
 23. The leukocyte-removing filtermaterial according to claim 1, wherein the reticulate structure is auniform reticulate structure.
 24. A process for producing aleukocyte-removing filter material which comprises dispersing fibershaving an average fiber diameter of not less than 0.01 μm but less than1.0 μm in a dispersion medium, and keeping the same, by paper-making, ona porous element having an average pore diameter of not less than 1.0 μmbut less than 100 μm, wherein the filter material consists of the porouselement and a fiber structure composed of a plurality of the fibers; theporosity of the filter material is not less than 50% but less than 95%;the keeping proportion of the fiber structure to the filter material isnot less than 0.01% by weight but less than 30% by weight; the ratiobetween the average pore diameter of the porous element and the averagefiber diameter of the fiber structure is not less than 2 but less than2,000; and the fiber structure forms a reticulate structure.
 25. Theproduction process according to claim 24, wherein the fibers having anaverage fiber diameter of not less than 0.01 μm but less than 1.0 μm arethose obtained by cleaving cleavable fibers.
 26. The production processaccording to claim 25, wherein the cleavable fibers are regeneratedcellulose fibers.
 27. The production process according to claim 26,wherein the method of cleaving the cleavable fibers is a fibrillationmethod.
 28. The production process according to claim 24, which furthercomprises a step in which the fibers having an average fiber diameter ofnot less than 0.01 μm but less than 1.0 μm are obtained by culturing amicroorganism having an ability to produce cellulose in a liquid culturemedium by intermittently or continuously applying a vibration theretoand recovering the fibers from the culture medium.
 29. The productionprocess according to claim 28, which further comprises a step ofsplitting the fibers recovered.
 30. The production process according toclaim 24, which further comprises a step in which the fibers having anaverage fiber diameter of not less than 0.01 μm but less than 1.0 μm areobtained by splitting the microorganism-cellulose fiber mass.
 31. Theprocess for producing a leukocyte-removing filter material according toclaim 24, which comprises dispersing the fibers having an average fiberdiameter of not less than 0.01 μm but less than 1.0 μm in a dispersionmedium to obtain a fiber dispersion, keeping this dispersion, bypaper-making, on a porous element having an average pore diameter of notless than 1.0 μm but less than 100 μm and subsequently subjecting theresulting filter material to a high pressure liquid treatment.
 32. Aprocess for producing a leukocyte-removing filter material whichcomprises allowing a microorganism having an ability to producecellulose fiber and a porous element having an average pore diameter ofnot less than 1.0 μm but less than 100 μm in a liquid culture medium,culturing the microorganism in the liquid culture medium, and thenrecovering the porous element, wherein the filter material consists ofthe porous element and a fiber structure having an average fiberdiameter of not less than 0.01 μm but less than 1.0 μm; the porosity ofthe filter material is not less than 50% but less than 95%; the keepingproportion of the fiber structure to the filter material is not lessthan 0.01% by weight but less than 30% by weight; the ratio between theaverage pore diameter of the porous element and the average fiberdiameter of the fiber structure is not less than 2 but less than 2,000;and the fiber structure forms a reticulate structure.
 33. The productionprocess according to claim 32, wherein the microorganism having anability to produce cellulose fiber is an acetic acid bacterium.
 34. Theproduction process according to claim 32, wherein the culture is astationary culture.
 35. The production process according to claim 32,wherein the liquid level of the liquid culture medium is intermittentlyor continuously changed to be allowed to pass through the exterior andinterior of the porous element, thereby culturing the microorganism. 36.The production process according to claim 32, wherein the microorganismis cultured while a gas is introduced into the liquid culture mediumand/or the interior of the porous element.
 37. The production processaccording to claim 32, which further comprises a step of turning theporous element upside down during the culture.
 38. The productionprocess according to claim 32, wherein the microorganism is cultured ata microorganism concentration of not less than one cells/mL but lessthan 1.0×10⁷ cells/mL.
 39. The production process according to claim 32,wherein the culturing time is not less than 0.5 hour but less than 48hours.
 40. A process for producing a leukocyte-removing filter materialwhich comprises spinning a porous element having an average porediameter of not less than 1.0 μm but less than 100 μm by a melt-blowmethod and mixing fibers having an average fiber diameter of not lessthan 0.01 μm but less than 1.0 μm into a fiber bundle stream which isbeing spun, wherein the filter material consists of the porous elementand a fiber structure composed of a plurality of fibers kept on theporous element, the porosity of the filter material is not less than 50%but less than 95%; the keeping proportion of the fiber structure to thefilter material is not less than 0.01% by weight but less than 30% byweight; the ratio between the average pore diameter of the porouselement and the average fiber diameter of the fiber structure is notless than 2 but less than 2,000; and the fiber structure forms areticulate structure.
 41. The production process according to claim 40which comprises a step of further subjecting the porous element and thefiber structure kept on the above porous structure to high pressureliquid treatment.
 42. An apparatus for removing leukocyte from aleukocyte-containing solution, which comprises 1) a feed opening, 2) afilter material which is composed of a porous element having an averagepore diameter of not less than 1.0 μm but less than 100 μm and a fiberstructure having an average fiber diameter of not less than 0.01 μm butless than 1.0 μm kept on the porous element and which has a porosity ofnot less than 50% but less than 95%, and in which filter material thekeeping proportion of the fiber structure to the filter material is notless than 0.01% by weight but less than 30% by weight, the ratio betweenthe average pore diameter of the porous element to the average fiberdiameter of the fiber structure is not less than 2 but less than 2,000and the fiber structure forms a reticulate structure; and 3) adischarging opening.
 43. The apparatus according to claim 42, wherein aplurality of sheets of the filter material are laminated in the flowdirection.
 44. The apparatus according to claim 42, wherein on the upperstream side and/or the down stream side of the filter material, otherfilter materials are arranged.
 45. The apparatus according to claim 44,which comprises a filter material for removing fine agglomerates on theupper stream side of the filter material.
 46. The apparatus according toclaim 42, wherein the sectional area of the filter material in thenormal line direction to the flow direction is not less than 3 cm² butless than 100 cm².
 47. A process for removing leukocyte from aleukocyte-containing solution, which comprises using an apparatus whichcomprises 1) a feed opening, 2) a filter material which is composed of aporous element having an average pore diameter of not less than 1.0 μmbut less than 100 μm and a fiber structure having an average fiberdiameter of not less than 0.01 μm but less than 1.0 μm kept on theporous element and which has a porosity of not less than 50% but lessthan 95% and in which filter material the keeping proportion of thefiber structure to the filter material is not less than 0.01% by weightbut less than 30% by weight, the ratio between the average pore diameterof the porous element to the average fiber diameter of the fiberstructure is not less than 2 but less than 2,000 and the fiber structureforms a reticulate structure; and 3) a discharging opening; pouring theleukocyte-containing solution to the feed opening; and recovering aliquid filtered by the filter material from the discharging opening. 48.The process according to claim 47, wherein the leukocyte-containingsolution is a whole blood preparation, a concentrated erythrocytepreparation or a platelet concentrate preparation.
 49. The processaccording to claim 48, wherein the leukocyte-containing solution is awhole blood preparation or a concentrated erythrocyte preparation andthe apparatus volume is not less than 3 mL but less than 20 mL per oneunit.
 50. The process according to claim 49, wherein theleukocyte-containing solution is a whole blood preparation or aconcentrated erythrocyte preparation and the number of the remainingleukocytes in the recovered solution is less than 1×10³ cells/unit. 51.The process according to claim 48, wherein the leukocyte-containingsolution is a platelet concentrate preparation and the apparatus volumeper 5 units is not less than 1 mL but less than 10 mL.
 52. The processaccording to claim 51, wherein the leukocyte-containing solution is aplatelet concentrate preparation and the number of the remainingleukocytes in the recovered solution is less than 1×10³ cells/5 units.53. The process according to claim 47, wherein the leukocyte-containingsolution is a body fluid, the leukocyte-containing solution iscontinuously introduced to the feed opening and a liquid filtered by thefilter is recovered from the discharge opening.